Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :1.0002167 |
This finding reinforces the biological significance of this predicted model and suggests that RAG 1 interacts with RAG 2 on one of the side of the scaffold formed by the beta propeller . . 1.0002167^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.54407654 |
However , both mutations reduce the capacity of RAG 2 to interact with RAG 1 and block recombination signal cleavage , therefore implicating a defect in the early steps of the recombination reaction as the basis of the clinical phenotype . 0.54407654^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.65210829 |
RSS induced conformational changes of StrRAG 1 may influence the interaction of RAG 1 with RAG 2 and synaptic complex formation . . 0.65210829^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.55501808 |
Amino acid residues in RAG 1 responsible for the interaction with RAG 2 during the 5 ( D ) J recombination process . 0.55501808^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Human RAG 2 , like RAG 1 , is on chromosome 11 band p 13 and therefore not linked to ataxia telangiectasia complementation groups . ^^^ Here we report the location of a human recombination activating gene ( RAG 2 ) , in addition to RAG 1 , on chromosome 11 , band p 13 , thereby formally demonstrating linkage of these genes in humans and showing that they are not linked to the known locus responsible for the A T syndrome . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Furthermore , the recombination activating genes RAG 1 and RAG 2 are differentially expressed , with RAG 2 detectable only by polymerase chain reaction , implying that very low levels of one of these gene products are sufficient to complement the other to facilitate VJ rearrangements . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Thus , the surface expression of an alpha beta TCR does not prevent further alpha TCR rearrangement in immature thymocytes that still transcribe RAG 1 and RAG 2 genes . ^^^ Reduced levels of RAG 1 and RAG 2 RNA are detectable only in CD4+8+ TCR high cells , which result from positive selection in the thymus . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
EBV DNA positive and negative HD cases with numerous SR cells lack significant mRNA expression of the two recombinase activating genes ( RAG 1 and RAG 2 ) . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Stable hybrids between the scid pre B and the myeloma cells had lost the expression of RAG 1 and RAG 2 genes , supporting the previous finding of an inhibitor of rearrangement in myeloma cells that acts shortly after fusion . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Northern ( RNA ) blot analysis of the expression of the MB 1 , lambda 5 , Vpre B , c mu , RAG 1 , and RAG 2 genes in pro B and pre B clones show that transcription of the MB 1 gene precedes IgH gene rearrangement and RNA synthesis from c mu , RAG 1 , RAG 2 , lambda 5 , and Vpre B genes . ^^^ All clones at the pre B cell stage synthesize mRNA for c mu , RAG 1 , and RAG 2 genes ; transcription of the lambda 5 and Vpre B genes seems to start after D to JH rearrangement in B cell precursors , indicating that the proteins encoded by either gene are not required for B cell progenitors to undergo D to JH gene rearrangement . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
In TCR / CD3 thymocytes , CD 2 stimulation also failed to affect steady state mRNA levels of the recombination activating genes RAG 1 and RAG 2 , whereas in TCR / CD3+ cells activation of the CD 2 pathway terminated their expression . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The recombination activating genes RAG 1 and RAG 2 are required for 5 ( D ) J DNA rearrangements at loci for immunoglobulin and T cell receptor genes . ^^^ Mapping analysis of RAG 1 and RAG 2 genes on human chromosomes by fluorescence in situ hybridization indicated that the genes are located on chromosome 11p13 p 12 . ^^^ RAG 1 and RAG 2 do not seem to be linked to any of the primary immunodeficiencies for which defective genes have already been mapped . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Expression of human recombination activating genes ( RAG 1 and RAG 2 ) in Hodgkin ' s disease . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The 5 ( D ) J recombinase activating genes , RAG 1 and RAG 2 , are coexpressed only in immature lymphocytes , and are sufficient and necessary for 5 ( D ) J recombination to occur in non lymphoid cells . ^^^ In order to examine control mechanisms operative in the regulation of RAG 1 and RAG 2 , we have studied the pattern of expression of these genes in human pre T cells , pre B cells , and thymocytes treated with the phorbol ester 12 O tetradecanoylphorbol 13 acetate ( TPA ) ; an agent which mimics some of the lymphocyte maturation changes seen in vivo . ^^^ The expression of RAG 1 and RAG 2 was tightly controlled in a rapid , yet very complex , manner with both positive and negative control elements operating . ^^^ Treatment of immature lymphocytes with TPA caused the specific and rapid elimination of steady state RAG 1 and RAG 2 RNA . ^^^ A labile transcriptional repressor , separate from the TPA associated repression of transcription , was also active in cells transcribing RAG 1 and RAG 2 RNA . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Activation of 5 ( D ) J recombination by RAG 1 and RAG 2 . 5 ( D ) J recombination is normally limited to lymphoid cells , but expression of the RAG 1 and RAG 2 genes allows other cell types to carry out this reaction . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Using a transient transfection assay , we demonstrate that the recombination activating genes Rag 1 and Rag 2 direct site specific rearrangement on an artificial substrate in poorly differentiated as well as in differentiated nonlymphoid cell lines . ^^^ N region insertions , which are characteristic of adult junctional diversity , are obtained at high frequency upon transfection of a terminal deoxynucleotidyltransferase expression vector together with Rag 1 and Rag 2 . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The RAG 1 and RAG 2 genes synergistically confer VDJ recombinase activity to nonlymphoid cell lines . ^^^ Levels of RAG 1 and RAG 2 expression in primary murine lymphoid tissues and lymphoid bone marrow cultures generally are much higher than those of transformed precursor B cell lines . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
In an attempt to determine the distribution of recombinase activity in the mouse thymus , spleen and lymph nodes , we used the in situ hybridization method to examine the expression of the recombination activating genes RAG 1 and RAG 2 . ^^^ Although hybridization signals of RAG 2 were not as intense as those of RAG 1 , the localization of RAG 2 transcripts was similar to that of RAG 1 . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Evidence was obtained for genetic linkage between the T 160 gene and the recombination activator genes RAG 1 and RAG 2 . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Two tightly linked recombination activating genes , RAG 1 and RAG 2 , are involved in VDJ recombination of the immune system . ^^^ It remains to be seen whether expression of RAG 1 and RAG 2 in CNS is abortive or functionally important . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The effect of cAMP agonists on recombination appears to reflect an increase in cellular recombination activity , as indicated by the caffeine induced rise in the level of mRNA from the recombination activating genes RAG 1 and RAG 2 . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Germ line kappa light chain gene transcription and rearrangement were unaffected , but transcription of the recombination activating genes RAG 1 and RAG 2 and the lymphoid specific transcription factor Oct 2 was increased . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The recombination activating genes , RAG 1 and RAG 2 , are on chromosome 11p in humans and chromosome 2p in mice . ^^^ The recombination activating genes RAG 1 and RAG 2 are adjacent genes that act synergistically to activate variable diversity joining ( 5 ( D ) J ) recombination . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Thymocyte expression of RAG 1 and RAG 2 : termination by T cell receptor cross linking . ^^^ The expression of the 5 ( D ) J [ variable ( diversity ) joining elements ] recombination activating genes , RAG 1 and RAG 2 , has been examined during T cell development in the thymus . ^^^ In situ hybridization to intact thymus and RNA blot analysis of isolated thymic subpopulations separated on the basis of T cell receptor ( TCR ) expression demonstrated that both TCR and TCR+ cortical thymocytes express RAG 1 and RAG 2 messenger RNA ' s . ^^^ Thus , although cortical thymocytes that bear TCR on their surface continue to express RAG 1 and RAG 2 , it appears that the expression of both genes is normally terminated during subsequent thymic maturation . ^^^ Consistent with this hypothesis , thymocyte TCR cross linking in vitro led to rapid termination of RAG 1 and RAG 2 expression , whereas cross linking of other T cell surface antigens such as CD 4 , CD 8 , or HLA class 1 had no effect . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
We report here that B cell lines derived from these tumors , as well as a line derived from 5 myc retroviral transformation , simultaneously express surface immunoglobulin ( a hallmark of mature B cells ) as well as a common subset of genes normally restricted to the pre B stage of development including the recombinase activating genes RAG 1 and RAG 2 . ^^^ Continued RAG 1 and RAG 2 expression in these lines is associated with VDJ recombinase activity detected with a VDJ recombination substrate . ^^^ Cross linking of the surface immunoglobulin on these lines with an anti mu antibody leads to rapid , specific and reversible down regulation of RAG 1 and RAG 2 gene expression . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Therefore , we have examined the potential role of the 5 ( D ) J recombination activating genes , RAG 1 and RAG 2 , in regulating chicken Ig gene conversion . ^^^ In contrast to the coexpression of RAG 1 and RAG 2 observed in mammalian B cells that undergo 5 ( D ) J recombination , chicken B cells isolated from the bursa of Fabricius express high levels of the RAG 2 mRNA but do not express RAG 1 mRNA . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
A simple technique for generating probes for RNA in situ hybridization : an adjunct to genome mapping exemplified by the RAG 1 / RAG 2 gene cluster . ^^^ As an example , we show that mRNA for the recombination activating genes ( RAG ) RAG 1 and RAG 2 is found in thymus of dE 16 mouse embryos . ^^^ Within the thymus , high levels of expression of RAG 1 and RAG 2 are detectable in the cortex but not in the medullary region . ^^^ This supports the view that RAG 1 and RAG 2 expression is associated with cells known to actively rearrange antigen receptor loci . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Expression of human recombination activating genes ( RAG 1 and RAG 2 ) in neoplastic lymphoid cells : correlation with cell differentiation and antigen receptor expression . ^^^ Recently , two genes , RAG 1 and RAG 2 , that are able to activate rearrangement of synthetic recombination substrates were cloned in mouse and a human gene homologous to RAG 1 was described . ^^^ To define the differentiation stages corresponding to RAG 1 and RAG 2 RNA expression , we have studied a large number of B and T lymphoid neoplasias . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Two recently cloned genes , RAG 1 and RAG 2 , are sufficient to induce rearrangements of synthetic substrates when transfected into fibroblasts . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Stable pre B cell 10 myeloma hybrids that retained the critical myeloma chromosomes were found to have lost VDJ recombinase activity and transcripts of the RAG 1 , RAG 2 and TdT genes . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Among three mRNAs encoding putative recombinase proteins , RAG 1 and RAG 2 mRNAs were not expressed in any cell lines tested , while RBP 2 mRNA was expressed ubiquitously . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The recombination activating genes , RAG 1 and RAG 2 , are likely to encode components of the 5 ( D ) J site specific recombination machinery . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Although several groups have shown that such a signal may be required to down regulate RAG 1 and RAG 2 after a functional Ag receptor has been generated in early mature T or B cells , recently it has been suggested that under some circumstances , cross linking the B cell Ag receptor may result in up regulation of RAG expression . ^^^ To study this possibility , we used a unique set of cell variants isolated from a human mature B cell line , which differ in their expression of both the surface Ig receptor ( sIg ) and RAG 1 and RAG 2 genes . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 , adjacent genes that synergistically activate 5 ( D ) J recombination . ^^^ RAG 1 inefficiently induced 5 ( D ) J recombinase activity when transfected into fibroblasts , but cotransfection with an adjacent gene , RAG 2 , has resulted in at least a 1000 fold increase in the frequency of recombination . ^^^ The 2 . 1 kilobase RAG 2 complementary DNA encodes a putative protein of 527 amino acids whose sequence is unrelated to that of RAG 1 . ^^^ Like RAG 1 , RAG 2 is conserved between species that carry out 5 ( D ) J recombination , and its expression pattern correlates precisely with that of 5 ( D ) J recombinase activity . ^^^ RAG 1 and RAG 2 might activate the expression of the 5 ( D ) J recombinase but , more likely , they directly participate in the recombination reaction . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 : nuclear genes involved in the dependence / independence on mitochondrial respiratory function for growth on sugars . ^^^ This phenotype was found to be controlled by two unlinked nuclear genes : RAG 1 and RAG 2 . ^^^ Either of their recessive alleles , rag 1 and rag 2 , led to the Rag phenotype ( i . e . the failure of growth on glucose in the presence of antimitochondrial drugs ) . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Epstein Barr virus induction of recombinase activating genes RAG 1 and RAG 2 . ^^^ In experimental B cell infections , Epstein Barr virus induced sustained expression of 5 ( D ) J recombinase activating genes RAG 1 and RAG 2 , whose aberrant activity has been implicated in chromosomal translocations in B cell neoplasms . ^^^ In cell lines in which RAG 1 and RAG 2 were detected , virus integrated into cellular DNA rather than assumed the configuration of extrachromosomal episomes . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
A regulatory role for recombinase activating genes , RAG 1 and RAG 2 , in T cell development . ^^^ RAG 1 and RAG 2 are developmentally regulated genes that are essential for the assembly of antigen receptors in lymphoid cells . ^^^ Here we describe transgenic mice that carry RAG 1 and RAG 2 under the control of the proximal lck promoter . ^^^ Persistent expression of RAG 1 and RAG 2 was associated with incomplete thymopoiesis and profoundly compromised cellular immunity . ^^^ These effects required both RAG 1 and RAG 2 , since mice that carried either gene exclusively were indistinguishable from wild type controls . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Of 16 agents tested , only interleukin 7 ( IL 7 ) induced 5 ( D ) J gene rearrangement and sustained expression of the RAG 1 and RAG 2 genes , which are known to control rearrangement . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Despite the essential and synergistic functions of the rag 1 and rag 2 proteins in 5 ( D ) J recombination and lymphocyte development , little is known about the biochemical properties of the two proteins . ^^^ Furthermore , the presence of rag 1 alters the behavior of rag 2 , conferring on it properties similar to those of rag 1 and changing its distribution in the nucleus . ^^^ We demonstrate that rag 1 and rag 2 are present in the same complex by coimmunoprecipitation , and we provide evidence that these complexes contain more molecules of rag 2 than of rag 1 . ^^^ The demonstration of intracellular complexes containing rag 1 and rag 2 raises the possibility that interaction between these proteins is necessary for their biological function . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Down regulation of RAG 1 and RAG 2 gene expression in preB cells after functional immunoglobulin heavy chain rearrangement . ^^^ The gene products of two recombination activating genes , RAG 1 and RAG 2 are crucial for this rearrangement process . ^^^ Here , we show that the expression of the RAG genes is twice up and down regulated , at the transcriptional level for RAG 1 and RAG 2 , and at the postranscriptional level for RAG 2 protein . ^^^ In immature B cells expressing on the cell surface RAG 1 and RAG 2 mRNA is down regulated , whereas RAG 2 protein levels are maintained . ^^^ Down regulation of RAG 1 and RAG 2 gene expression after productive rearrangement at one heavy chain allele might be part of the mechanisms that prevent further rearrangements at the other allele . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Our results show that a full length TCR delta transcript and the recombination activating genes RAG 1 and RAG 2 mRNA were already expressed in the CD34+1 subset . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
When used to drive expression of the recombination activating genes 1 and 2 ( RAG 1 and RAG 2 ) , the autoregulatory system yielded both substantially higher levels of variable ( diversity ) joining [ 5 ( D ) J ] recombination activity ( 70 fold on average ) and inducible expression in a much larger fraction of transfected cells ( autoregulatory , 90 % , vs . constitutive , 18 % ) . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
One genomic clone , lambda 4 , contained two RA genes , RAG 1 and RAG 2 . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Reflecting extrathymic T cell differentiation , MNC in the liver and pregnant uterus expressed mRNA of RAG 1 and RAG 2 . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
These results suggest that RAG 1 and RAG 2 are components of the 5 ( D ) J recombinase . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Expression of recombination activating genes ( RAG 1 and RAG 2 ) in Epstein Barr virus bearing B cells . ^^^ Recombination activating genes 1 and 2 ( RAG 1 and RAG 2 ) , are the only lymphoid specific genes required for the site directed recombination reaction leading to generation of B cell receptors and T cell receptors ( TCRs ) . ^^^ In EBV+ Burkitt ' s lymphoma lines , transcription of virus latent membrane protein 1 ( LMP 1 ) was correlated with downregulation of RAG 1 and RAG 2 . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
This rescue of scid B cell differentiation is associated with a dramatic reduction in expression of the recombination activation genes , RAG 1 and RAG 2 , and with reduced transcription of the kappa locus . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
In the postnatal period , both RAG 1 and RAG 2 genes are expressed at high levels in the RPL population . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
In a model system , RAG 1 and RAG 2 , the genes responsible for activating 5 ( D ) J recombination , were identified in a genomic transfectant by cDNA RDA in a small fraction of the time taken by conventional means . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Coordinate expression of two structurally distinct recombinase activating genes , RAG 1 and RAG 2 , is necessary for activation of site specific 5 ( D ) J recombination . ^^^ In mice bearing targeted disruptions of either the RAG 1 or RAG 2 genes , T and B lymphocyte development is arrested at the CD 4 8 double negative ( DN ) thymocyte or B220+ / CD43+ pro B cell stage . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Expression of human recombination activating genes ( RAG 1 and RAG 2 ) in lymphoma . ^^^ Two recently discovered genes , the recombination activating genes 1 and 2 ( RAG 1 and RAG 2 ) , are necessary to perform variable ( 5 ) , diversity ( D ) , and joining ( J ) recombination . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 expression in human intestinal epithelium : evidence of extrathymic T cell differentiation . ^^^ When T lymphocytes undergo gene rearrangement , the products of both RAG 1 and RAG 2 genes are expressed ; RAG mRNA is present only in tissue governing lymphocyte maturation . ^^^ In this study , reverse transcription polymerase chain reaction ( RT PCR ) was used to detect RAG 1 and RAG 2 specific mRNA . ^^^ Primers for first round and nested PCR of RAG 1 and RAG 2 were synthesized . ^^^ RAG 1 and RAG 2 mRNA was detected in all bone marrow preparations but was absent in all peripheral blood samples . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 gene expression and 5 ( D ) J recombinase activity are enhanced by protein phosphatase 1 and 2A inhibition in lymphocyte cell lines . ^^^ Expression of the recombination activating genes , RAG 1 and RAG 2 , in lymphocytes , has been shown to depend on second messenger systems . ^^^ The cell permeable tumor promoter , calyculin A ( CLA ) , which is a potent inhibitor of the type 1 and 2A serine / threonine protein phosphatases ( PP 1 and PP2A , respectively ) , was shown to upregulate the expression of RAG 1 and RAG 2 in pre B as well as mature B and T lymphocyte cell lines . ^^^ Moreover , in these mature lymphocyte cell lines there was no evidence of synergy in the regulation of RAG 1 and RAG 2 mRNA upon stimulation with CLA and caffeine . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
These events are accompanied by marked increases in the expression of RAG 1 and RAG 2 RNAs . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The recombinase activating genes , RAG 1 and RAG 2 , have been shown to be necessary to initiate the process of 5 ( D ) J recombination during the ontogeny of lymphocytes . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Recombinase activating genes ( RAG 1 and RAG 2 ) are expressed in immature T or B lymphocytes and possess activity to induce 5 ( D ) J rearrangement in TCR and Ig genes . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 are developmentally regulated genes that are essential for 5 ( D ) J recombination and lymphocyte development . ^^^ Expression of RAG 1 and RAG 2 by thymocytes is normally limited to cells that have not completed selection . ^^^ We find that neither selection nor TCR allelic exclusion can be overcome by transgenic expression RAG 1 and RAG 2 under the control of an lck promoter . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 are lymphoid specific genes that together induce 5 ( D ) J recombinase activity in a variety of nonlymphoid cell types . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
This process is highly regulated and mediated by the recombination activating proteins RAG 1 and RAG 2 . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
This event is accompanied by several changes classically associated with light chain gene rearrangement including increased activity of the NF kappa B transcription factor , expression of light chain RNAs and increased levels of expression of the RAG 1 and RAG 2 genes . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Although RAG 1 and RAG 2 have been shown to be indispensible for 5 ( D ) J recombination , their exact role in this reaction remains unclear . ^^^ Co transfecting RAG 1 and RAG 2 expression vectors into NIH3T3 fibroblasts confers 5 ( D ) J recombination activity to these otherwise recombinationally inactive cells . ^^^ In this report we have found that in transient transfections of mouse NIH3T3 fibroblasts with RAG 1 and RAG 2 and the appropriate recombination substrates , one RAG 1 expression vector , pRAG 1A , is capable of yielding both signal joints and coding joints , while another RAG 1 expression vector , pRAG 1B , yields only signal joints . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
These lymphoid cells expressed transcripts of the recombination activating genes , RAG 1 and RAG 2 , as well as the C mu gene , although the lymphoid cells did not express surface antigens specific to T or B lymphocytes such as T 200 , CD 4 , CD 8 and B 220 , or transcripts of B lymphocyte specific genes such as lambda 5 and mb 1 . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
We have assayed the 5 3 Chinese hamster ovary cell line , which has a double strand DNA break repair ( dsbr ) defect , for the ability to carry out 5 ( D ) J recombination following transfection of constructs that encode the RAG 1 and RAG 2 proteins necessary to confer 5 ( D ) J recombination activity to non lymphoid cells . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The products of the RAG 1 and RAG 2 genes are essential for the recombination of the DNA encoding the antigen receptors of the developing immune system . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
TCR rearrangement strictly depends upon the coordinate activity of two recombinase activating genes , Rag 1 and Rag 2 . ^^^ The results indicate that there are two periods of high Rag 1 and Rag 2 mRNA expression . ^^^ Active downregulation of Rag 1 and Rag 2 mRNA expression appears to occur in vivo between the two peaks of recombinase activity . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The recombination activating proteins RAG 1 and RAG 2 are both essential for this process , termed 5 ( D ) J rearrangement . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Unexpectedly , we found that overexpression of the FL zeta chain caused premature termination of RAG 1 and RAG 2 expression , prevented productive rearrangement of the TCR alpha and TCR beta genes and blocked entry of thymocytes into the CD4 / CD8 developmental pathway . ^^^ These results suggest that an early signaling pathway exists in precursor TCR thymocytes that can regulate RAG 1 and RAG 2 expression and is differentially responsive to individual members of the zeta family dimers . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Most significantly , the genes RAG 1 and RAG 2 , which are necessary for T cell receptor gene recombination to occur , are not expressed in liver T cells . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
While the parental cell line expressed low levels of the recombination activating genes , RAG 1 and RAG 2 , expression of these genes were considerably upregulated in both the immunoglobulin negative and the idiotypic variants . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Either RAG 1 or RAG 2 gene was not expressed in the B SCID derived cell lines . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The products of the RAG 1 and RAG 2 genes cooperate to allow 5 ( D ) J recombination in lymphoid and non lymphoid cells . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The recombinase activating genes RAG 1 and RAG 2 operate together to activate 5 ( D ) J recombination , and thus play an essential role in the generation of immune system diversity . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
We also show that IL 7 induced RAG 1 and RAG 2 mRNA expression by FL cells . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
In spite of the fact that CD 4 plays a critical role in thymocyte development , the abnormal signaling does not appear to influence thymocyte development at the stage when the T cell receptor is rearranged and the recombinase enzymes RAG 1 and RAG 2 transcripts are downregulated . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
In addition , detection of these broken ended signal sequences is dependent on the activity of RAG 1 and RAG 2 , and is restricted to the G0 / G1 phase of the cell cycle . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
No relationship of DSB rejoining to 5 ( D ) J recombinase activity was observed , since no mRNA hybridizing to the cDNA probes for RAG 1 or RAG 2 was detected in any of the cell lines tested . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 are not sufficient to direct all phases of immunoglobulin gene rearrangement in pre B cell lines . ^^^ Introduction of the RAG 1 and RAG 2 genes , genes encoding two such factors , failed to confer a rechi phenotype to these cells . ^^^ Neither the rechi phenotype nor kappa chain rearrangement correlated with levels of RAG 1 and RAG 2 expression in all of the hybrids . ^^^ Thus , both gene transfer and cell fusion experiments indicate that RAG 1 and RAG 2 are not sufficient to activate immunoglobulin gene recombination in at least some pre B cell lines . ^^^ In addition , the fusion experiments suggest that two gene products in addition to RAG 1 and RAG 2 may be required for kappa gene rearrangement . . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Northern analysis demonstrated that while the expression of the recombination activating genes RAG 1 and RAG 2 was relatively low in the parental cell line , their expression was significantly increased in both the sIg variants and their sIg+ progenies . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
R PCR also demonstrates expression of lambda 5 , RAG 1 and RAG 2 , which are specifically associated with pre B stage lymphocytes . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Dispensable sequence motifs in the RAG 1 and RAG 2 genes for plasmid 5 ( D ) J recombination . ^^^ As a probe of whether RAG 1 and RAG 2 gene products activate other genes or form part of the recombinase itself , certain mutants of the RAG genes were assayed for their ability to activate variable diversity joining region [ 5 ( D ) J ] recombination in a plasmid substrate in fibroblasts . ^^^ The results indicate that the N terminal one third of RAG 1 , including a zinc finger like domain , and an acidic domain of RAG 2 are dispensable for activating 5 ( D ) J recombination in a fibroblast , although they contribute quantitatively . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Transfection of fibroblasts from transgenic and control mice with the recombination activating genes , Rag 1 and Rag 2 , led to a high level of rearrangement of the hypomethylated transgenic , but not the endogenous chi genes . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Rag 1 and Rag 2 expression is also tightly regulated , and is found largely in the Pro B through small Pre B stages . ^^^ In contrast , lambda 5 , VpreB , Rag 1 , and Rag 2 are expressed at comparable levels . . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The recombination activating genes RAG 1 and RAG 2 appear to be necessary components of the machinery needed for the Ig or TCR gene rearrangements that occur in developing B and T lymphocytes . ^^^ Because gene conversion may be an important mechanism for 5 gene diversification in the rabbit , we cloned the rabbit RAG locus and characterized the coding regions of the genomic RAG 1 and RAG 2 . ^^^ In addition , we sequenced cDNAs encompassing the RAG 2 coding region , part of the RAG 2 5 ' untranslated region and a 967 bp fragment of cDNA from the RAG 1 coding region . ^^^ Northern analysis revealed a RAG 1 mRNA of 6 . 6 kb which is similar in size to the RAG 1 mRNA reported previously for other species , and a major species of RAG 2 mRNA of 4 . 4 kb , which is larger than that from the mouse ( 2 . 2 kb ) . ^^^ Analysis of the genomic clones showed that , as in other species , the RAG 1 and RAG 2 genes are oriented so as to be convergently transcribed . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Moreover , the expression of recombination activating genes 1 and 2 ( RAG 1 and RAG 2 ) also correlated with TCR gamma delta maturation as only HSA+ TCR gamma delta cells transcribed these genes . ^^^ Interaction of the HSA+ Tg+ TCR gamma delta cells with anti TCR gamma delta mAb or Ag bearing thymic stromal cells resulted in RAG 1 and RAG 2 down regulation . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Characterization and expression of recombination activating genes ( RAG 1 and RAG 2 ) in Xenopus laevis . ^^^ Two closely linked genes , RAG 1 and RAG 2 , are essential for this process , and have been identified in mice , humans , and chickens . ^^^ To study lymphocyte development in Xenopus laevis , we have characterized RAG 1 and RAG 2 in this species and examined their patterns of expression . ^^^ A product of expected size was obtained and used to identify a genomic clone that contained the complete coding region of RAG 1 ( 1045 codons ) , and approximately the 3 ' half of the coding region of RAG 2 . ^^^ The coding regions of RAG 1 and RAG 2 each lie on a single exon , are in opposite transcriptional orientation , and are separated by approximately 6 kb . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Here we show that early during the differentiation of pre B cells , upregulation of RAG 1 and RAG 2 expression go hand in hand with rearrangements of the Ig gene loci . ^^^ Moreover , the newly formed sIg+ B cells continue to express RAG 1 and RAG 2 and continue to rearrange L chain gene loci , even in the absence of proliferation , in an orderly fashion , so that kappa L+ sIg+ cells can become lambda L+ sIg+ or sIg cells , whereas lambda L+ sIg+ cells can become sIg , but not kappa L+ sIg+ cells . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Cortical thymocytes that express a TCR on their surface continue to express mRNA for the recombination activating genes RAG 1 and RAG 2 . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The disappearance of the broken DNA molecules occurs in the same developmental transition as termination of expression of the recombination activating genes , RAG 1 and RAG 2 . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Here we show that extracts made from a lymphoid cell line that expresses truncated forms of the Rag 1 and Rag 2 proteins have a signal cutting activity that obeys the 12 / 23 rule . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
In the first step of 5 ( D ) J recombination , the RAG 1 and RAG 2 proteins cleave DNA between a signal sequence and the adjacent coding sequence , generating a blunt signal end and a coding end with a closed hairpin structure . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
A transitional cell type has lost RAG 2 but not RAG 1 . ^^^ We have used a highly sensitive Northern blot probing technique to examine RAG 1 and RAG 2 mRNA expression in unmanipulated murine thymocytes of various developmental phenotypes sorted by flow cytometry . ^^^ We have found that neither RAG 1 nor RAG 2 are down regulated until thymocytes reach the TCRhi stage . ^^^ TCRhi , CD8+CD4+ cells have lost RAG 2 mRNA but continue to express significant levels of RAG 1 mRNA , providing molecular evidence that this cell type is transitional between the TCRlo , CD4+CD8+ and the TCRhi , CD4+CD8 , or CD 4 CD8+ phenotypes . . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Recombination activating genes Rag 1 and Rag 2 were isolated on the basis of their ability to confer 5 ( D ) J recombination activity when co expressed in fibroblasts . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
A large panel of cell lines deficient in DNA repair were tested for the ability to perform 5 ( D ) J recombination after introduction of the RAG 1 and RAG 2 genes . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The recombination activator genes RAG 1 and RAG 2 are essential for this process , termed 5 ( D ) J rearrangement . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
By contrast , we did not detect transcripts of the RAG 1 and RAG 2 genes , which are required for 5 ( D ) J recombination at gene loci for immunoglobulin and T cell receptors . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Expression of human recombination activating genes ( RAG 1 and RAG 2 ) in angioimmunoblastic lymphadenopathy and anaplastic large cell lymphoma of T type . ^^^ In order to determine the genotypic maturation status of the proliferating lymphoid cells in angioimmunoblastic lymphadenopathy ( AILD ) and in anaplastic large cell lymphoma of T type ( T ALC ) , recombinase activating gene ( RAG 1 and RAG 2 ) expression was assessed in six AILD and five T ALC cases using a sensitive reverse transcriptase ( RT ) and competitive ( C ) polymerase chain reaction ( PCR ) . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Cleavage at a 5 ( D ) J recombination signal requires only RAG 1 and RAG 2 proteins and occurs in two steps . ^^^ Here we show that purified RAG 1 and RAG 2 proteins are sufficient to carry out this reaction . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
B 17 SCID mouse or in RAG 1 ( recombination activating gene 1 ) or RAG 2 deficient mice . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The RAG 1 and RAG 2 proteins establish the 12 / 23 rule in 5 ( D ) J recombination . 5 ( D ) J recombination requires a pair of signal sequences with spacer lengths of 12 and 23 base pairs . ^^^ Cleavage by the RAG 1 AND RAG 2 proteins was previously shown to demand only a single signal sequence . ^^^ Coupled cutting at both sites requires only the RAG 1 and RAG 2 proteins , but depends on the metal ion . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The products of the recombination activating genes RAG 1 and RAG 2 are essential for activating 5 ( D ) J recombination , and thus are indispensable for the production of functional and diverse antigen receptors . ^^^ As defined previously , the core active regions of RAG 1 and RAG 2 permit the deletion of 40 % and 25 % , respectively , of well conversed sequence . ^^^ We show here that this `` dispensable ' ' region of RAG 1 is not necessary for coding joint formation or recombination of an integrated substrate , and this portion is not functionally redundant with the `` dispensable ' ' region of RAG 2 . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Recombination activating genes RAG 1 and RAG 2 , which are normally expressed during specific early stages of lymphocyte development , were expressed in not only the light chain shifting inducible lines but also in the non inducible cells . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The half life of RAG 1 protein in precursor B cells is increased in the absence of RAG 2 expression . ^^^ Site specific recombination of immunoglobulin and T cell receptor gene segments in B and T lymphocytes is dependent on the expression of two recombinant activation genes , Rag 1 and Rag 2 . ^^^ Here , we show that RAG 1 protein turnover in pre B cells depends on the expression of RAG 2 . ^^^ The apparent half life of RAG 1 protein is increased when RAG 2 is not expressed in differentiating pre B cells . . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Cleavage of 5 ( D ) J recombination signals by purified RAG 1 and RAG 2 proteins permits the dissection of DNA structure and sequence requirements . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
F3Ag DP thymocytes show a reduced expression of RAG 1 and RAG 2 compared with F3Ag+ DP cells . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Recombination activating gene 1 ( RAG 1 ) , as well as RAG 2 , are the only lymphoid specific genes required for 5 ( D ) J recombination . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Localization , interaction , and RNA binding properties of the 5 ( D ) J recombination activating proteins RAG 1 and RAG 2 . ^^^ The RAG 1 and RAG 2 gene products are indispensable for activating somatic rearrangement of antigen receptor gene segments . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The former has been rendered recombination competent by stable transfection of a genomic fragment comprising the recombination activating genes , RAG 1 and RAG 2 , along with some of their flanking sequences . ^^^ In both cell lines , recombinational activity reflects steady state levels of mRNA transcribed from the RAG 1 and RAG 2 genes . ^^^ A comparison of RAG 1 and RAG 2 mRNA levels within each cell line reveals almost identical response patterns indicating that RAG 1 and RAG 2 transcription is coordinately regulated . ^^^ Together , these results imply that the RAG containing fragment in L 4 fibroblasts carries most , if not all , control regions regulating the transcription of the RAG 1 and RAG 2 genes . . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Initiation of 5 ( D ) J recombinations in a cell free system by RAG 1 and RAG 2 proteins . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
rag 1 and rag 2 : biochemistry and protein interactions . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
This ability is conferred by the recombination activating genes 1 and 2 ( RAG 1 and RAG 2 ) . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Six of 14 B SCID patients tested were found to carry a mutation of the recombinase activating gene 1 ( RAG 1 ) , RAG 2 , or both . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Purified RAG 1 and RAG 2 proteins can cleave DNA at 5 ( D ) J recombination signals . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Transcription of the gene was reduced in the rag 1 , rag 2 , rag 5 and rag 8 mutants , which are defective for the low affinity glucose permease , phosphoglucose isomerase , hexokinase , and a positive regulator of RAG 1 expression , respectively . . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Semiquantitative RT PCR analysis performed on mononuclear bone marrow cells indicated that lambda like , VpreB , Rag 1 , Rag 2 , and TdT transcripts expressed during proB cell stages were found at normal levels whereas E2A , CD 10 , Syk , Pax 5 , CD 19 , Igalpha , Igbeta , VH Cmu , and Vkappa Ckappa transcripts characteristic of later stages were severely depressed . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
It was found that co transfection of Oct2A together with an artificial recombination substrate increased the rate of 5 ( D ) J recombination by a factor of 3 . 4 in the fibroblast cell line L 4 which had been stably transfected with genomic DNA containing the rag 1 and rag 2 genes and their flanking regulatory sequences . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
However , the latter are positive for recombination activating gene ( RAG 1 and RAG 2 ) mRNA , which are only expressed in the precursor or immature T cell lineage , and also possess CD 3 epsilon mRNA in their cytoplasm , suggesting that CD 3 epsilon ( dim ) NK T cells are the precursor of 5 alpha 14 NK T cells . . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 1 mediates signal sequence recognition and recruitment of RAG 2 in 5 ( D ) J recombination . ^^^ Recent studies have demonstrated that DNA cleavage during 5 ( D ) J recombination is mediated by the RAG 1 and RAG 2 proteins . ^^^ Here , we use an in vivo one hybrid DNA binding assay to demonstrate that RAG 1 , in the absence of RAG 2 , can mediate signal recognition via the nonamer , with the heptamer acting to enhance its binding . ^^^ Localization of RAG 2 to the signal is dependent upon the presence of RAG 1 and is substantially more efficient with a 12 bp spacer signal than with a 23 bp spacer signal . . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The 5 ( D ) J recombinase subunits Rag 1 and Rag 2 mediate assembly of antigen receptor gene segments . ^^^ We studied the mechanisms of DNA recognition by Rag 1 / Rag 2 using surface plasmon resonance . ^^^ Once the Rag 1 / Rag 2 complex is engaged on the DNA , subsequent cleavage is directed by the heptamer sequence . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The establishment of a functional immune system with diverse antigen receptors is dependent on the 5 ( D ) J recombination activating gene products Rag 1 and Rag 2 . ^^^ Both Rag 1 and Rag 2 are required for the catalysis of the initial stages of 5 ( D ) J recombination . ^^^ Thus , functional disruption of either the Rag 1 or Rag 2 genes by homologous recombination , leads to immunodeficiency due to lymphoid arrest at a stage prior to the recombination of the antigen receptor loci . ^^^ The Rag deficient background has been used as a system for : the functional analysis of Rag 1 and Rag 2 ; studying the developmental functions of antigen receptors and other molecules of the immune system ; the molecular analysis of the early stages of the B and T cell lineages ; the co development of lymphocytes with stroma cells ; the identification of minor subpopulations of the developing immune system ; the involvement of lymphoid populations in the onset of pathogenesis . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Illegitimate recombinase activity promoted by the recombination activating RAG 1 and RAG 2 is assumed to be involved in the pathogenesis of the chromosomal translocations observed in lymphoid neoplasias . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
A mutant RAG 1 gene which lacks a part of the topoisomerase 1 like region and a mutant RAG 2 gene which lacks its 89 C terminal amino acids did not activate 5 ( D ) J recombination in NIH 3T3 cells . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The recombinase activation genes , RAG 1 and RAG 2 , are expressed together in immature T or B lymphocytes and possess activity to induce 5 ( D ) J rearrangement in T cell receptor ( TCR ) and Ig genes . ^^^ In this study , we have used RAG 1 and RAG 2 genes as markers of possible genetic recombination in developing murine preimplantation embryos , using the highly sensitive reverse transcriptase polymerase chain reaction ( RT PCR ) technique and in situ hybridization . ^^^ A PCR of 35 cycles disclosed expression of RAG 1 but not RAG 2 in morulae and blastocysts . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Upon differentiation , proliferation ceases , and upregulation of Rag 1 and Rag 2 expression , and induction of 5 ( D ) J immunoglobulin gene rearrangements occur . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Reexpression of RAG 1 and RAG 2 genes in activated mature mouse B cells . ^^^ Recombination activating genes ( RAG 1 and RAG 2 ) , involved in 5 ( D ) J rearrangement of immunoglobulin genes , have been thought to be expressed only in immature stages of B cell development . ^^^ However , RAG 1 and RAG 2 transcripts were found to be reexpressed in mature mouse B cells after culture with interleukin 4 in association with several different co stimuli . ^^^ RAG 1 and RAG 2 proteins could be detected by immunofluorescence microscopy in the nuclei of B cells cultured in vitro and in the germinal centers of draining lymph nodes . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Neoteny in lymphocytes : Rag 1 and Rag 2 expression in germinal center B cells . ^^^ The products of the Rag 1 and Rag 2 genes drive genomic 5 ( D ) J rearrangements that assemble functional immunoglobulin and T cell antigen receptor genes . ^^^ Abundant RAG 1 and RAG 2 protein and messenger RNA was detected in the activated B cells that populate murine splenic and Peyer ' s patch germinal centers . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Interestingly , both RAG 1 and RAG 2 transcripts were also detected in this cell fraction , suggesting that sterile TCR transcription might be dependent upon the presence of a functional recombinase system . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The mRNA of RAG 1 , RAG 2 , Ku 80 , and terminal deoxynucleotidyl transferase ( TdT ) genes was equally detected between control and mutant thymi , suggesting that the expression of common recombination machinery is not affected . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Recent experiments have shown that cleavage is catalyzed by the RAG 1 and RAG 2 proteins and generates an asymmetric set of broken ends : hairpin coding ends and blunt signal ends . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Recent insights into the mechanism of 5 ( D ) J recombination have clarified the direct role of the products of the recombination activating genes Rag 1 and Rag 2 in site specific DNA cleavage at recombination signal sequences and have identified components of the general DNA double strand break repair pathway that participate in the rejoining of the Rag 1 and Rag 2 cut receptor gene segments . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The first step of 5 ( D ) J recombination , specific cleavage at the recombination signal sequence ( RSS ) , can be carried out by the recombination activating proteins RAG 1 and RAG 2 . ^^^ RAG 1 and RAG 2 alone or in combination were unable to generate signal joints . ^^^ However , RAG 1 and RAG 2 complemented with nuclear extracts were able to recombine an extrachromosomal substrate and form precise signal joints . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 in developing rabbit appendix subpopulations . ^^^ We found that the CD43+IgM and double negative CD 43 IgM cells contained RAG 1 transcripts and RAG 2 protein . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
A transient 5 ( D ) J recombination assay after the introduction of the RAG 1 and RAG 2 genes indicated that the 5 ( D ) J recombination ability of the CHO irs 20 cells was about 10 % of that for the CHO wild type cells for signal join formation with an 80 % joining fidelity and only 3 % of the parental level for coding join formation . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
IL 7 did not change the m RNA levels of the 5 ( D ) J recombination activating genes RAG 1 and RAG 2 , therefore IL 7 must exert its influence on 5 ( D ) J recombination either by post transcriptional regulation of the RAG genes or by the regulation of other genes that are involved in 5 ( D ) J recombination . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The RAG 1 and RAG 2 proteins initiate 5 ( D ) J recombination by making specific double strand DNA breaks at recombination signal sequences . ^^^ We show here that RAG 1 and RAG 2 bind specifically to this sequence , forming a stable protein DNA complex . ^^^ The complex requires the conserved heptamer and nonamer motifs of the recombination signal as well as both the RAG 1 and RAG 2 proteins . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Expression of the recombinase activating genes RAG 1 and RAG 2 was greatly reduced in the IL 7R alpha / thymuses , and in DN thymocytes from the TCR transgenic IL 7R alpha / mice , but was restored in double positive thymocytes from the TCR transgenic IL 7R alpha / mice . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Definition of a large region of RAG 1 that is important for coimmunoprecipitation of RAG 2 . ^^^ Interaction between the RAG 1 and RAG 2 proteins is probably critical for 5 ( D ) J recombination . ^^^ Using a coimmunoprecipitation assay , we define a large region of RAG 1 ( amino acids 504 1008 ) that is sufficient for interaction with RAG 2 . ^^^ Deletion of either of two regions of RAG 1 ( amino acids 504 570 or 850 1008 ) causes a loss of interaction with RAG 2 . ^^^ Loss of coimmunoprecipitation is also seen with RAG 1 core proteins containing deletions of smaller stretches of amino acids ( amino acids 506 511 or 545 550 ) , emphasizing the importance of this region of RAG 1 in forming a complex with RAG 2 . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 1 , RAG 2 and pre T cell receptor alpha chain expression by adult human hepatic T cells : evidence for extrathymic T cell maturation . ^^^ These were examined for molecular evidence of local T cell maturation using reverse transcription polymerase chain reaction to detect expression of recombination activation gene 1 ( RAG 1 ) , RAG 2 and pre T cell receptor alpha chain ( pTalpha ) , which occurs only in early thymocyte development . ^^^ Four specimens of whole liver were positive for RAG 1 and RAG 2 expression , whereas peripheral blood mononuclear cells from the same individuals were negative . ^^^ We detected the expression of RAG 1 , RAG 2 and pre TCRalpha in five specimens of hepatic CD2+CD7+ but not in CD45RO+ hepatic lymphocytes . ^^^ Four out of six specimens of CD2+CD7+ cells from the peripheral blood were negative for RAG 1 and RAG 2 while all six specimens were positive for pTalpha expression . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The proteins RAG 1 and RAG 2 are essential for initiation of 5 ( D ) J recombination . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Characterization and expression of the recombination activating genes ( rag 1 and rag 2 ) of zebrafish . ^^^ The closely linked recombination activating genes , rag 1 and rag 2 , encode components of the recombinase involved in 5 ( D ) J recombination of the immunoglobulin and T cell receptor genes . ^^^ We cloned the rag locus of the zebrafish Danio rerio and sequenced the open reading frames of the rag 1 and rag 2 genes . ^^^ Expression of both rag 1 and rag 2 begins late in embryonic development , on day 4 , by northern RNA blot analysis . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 form a stable postcleavage synaptic complex with DNA containing signal ends in 5 ( D ) J recombination . ^^^ During 5 ( D ) J recombination , RAG 1 and RAG 2 cleave DNA adjacent to highly conserved recombination signals , but nothing is known about the protein DNA complexes that exist after cleavage . ^^^ This complex includes the proteins RAG 1 , RAG 2 , HMG 1 or the closely related HMG 2 protein , and the components of the DNA dependent protein kinase . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
In three independently derived mouse strains lacking the recombination activating genes RAG 1 or RAG 2 , which are essential for Ig production , Ig ir was absent from the fetal CNS . ^^^ Western blot analyses of wild type brains from embryonic day 12 through birth identified a 25 kDa protein that co migrated with Ig light chain and was absent from RAG 1 or RAG 2 / brain samples . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
New work shows that the first step is a site specific cleavage which can be performed by purified RAG 1 and RAG 2 proteins . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The first stage of the reaction , which can be reproduced with the purified RAG 1 and RAG 2 proteins , is a site specific cleavage that generates the same broken DNA species found in vivo . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Products of recombination activating genes ( RAG 1 and RAG 2 ) involved in the rearrangement of Ig genes have been shown to be expressed only in immature stages of B cells . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
A complex of RAG 1 and RAG 2 proteins persists on DNA after single strand cleavage at 5 ( D ) J recombination signal sequences . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
To follow development of the immune system in zebrafish , we have analyzed the expression of the recombination activating genes , rag 1 and rag 2 , which we have previously isolated and characterized . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Truncated RAG 1 and RAG 2 proteins , while capable of cleaving at isolated RSS in cell free systems , also require a 12 / 23 RSS pair for efficient cleavage in vivo . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Proteins encoded by the RAG 1 and RAG 2 genes are responsible for the recognition and double stranded cleavage of a highly conserved DNA sequence flanking all rearranging gene segments . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The end joining reaction in 5 ( D ) J recombination . 5 ( D ) J recombination consists of a DNA cleavage reaction catalysed by RAG 1 and RAG 2 , followed by an end joining reaction that utilizes the cell ' s double strand break repair machinery . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Furthermore , the Ku 70 ( / ) cells lack the ability to effectively rejoin signal and coding ends liberated in transiently introduced 5 ( D ) J recombination substrates by enforced RAG 1 and RAG 2 expression . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Semi quantitative RT PCR analysis performed on mononuclear bone marrow cells from the non XLA patient indicated that lambda like , VpreB , Rag 1 , Rag 2 and TdT transcripts expressed during proB cell stages were found at normal levels whereas E2A , CD 10 , Syk , Pax 5 , CD 19 , Ig alpha , Ig beta , VH C mu and 5 kappa C kappa transcripts characteristic of later stages were severely depressed . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
V ( D ) J recombination : modulation of RAG 1 and RAG 2 cleavage activity on 12 / 23 substrates by whole cell extract and DNA bending proteins . ^^^ Recent studies have shown that this restriction operates at the level of DNA cleavage , which is mediated by the products of the recombination activating genes RAG 1 and RAG 2 . ^^^ Here , we show that RAG 1 and RAG 2 are not sufficient for 12 / 23 dependent cleavage , whereas RAG 1 and RAG 2 complemented with whole cell extract faithfully recapitulates the 12 / 23 rule . ^^^ In addition , HMG box containing proteins HMG 1 and HMG 2 enhance RAG 1 and RAG 2 mediated cleavage of substrates containing 23 RSS but not of substrates containing only 12 RSS . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Farage cells did not express the terminal deoxynucleotydyl transferase gene ( TdT ) , nor the recombination activating genes RAG 1 and RAG 2 , known as markers of the pre B cell stage . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The RAG 1 and RAG 2 proteins initiate the reaction by making double strand DNA breaks at both signals , and must thus be able to operate on these two different spatial arrangements . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 genes are transcriptionally active in fetal and adult IL 7R alpha / thymocytes . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
It is now clear that the RAG 1 and RAG 2 proteins play a direct role in DNA recognition and cleavage and that both RAG proteins are required for the nicking and strand transfer steps of the cleavage reaction . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The RAG 1 and RAG 2 proteins are the critical lymphoid cell specific components of the recombination enzymatic machinery and are responsible for site specific DNA recognition and cleavage . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The first step in DNA cleavage at 5 ( D ) J recombination signals by RAG 1 and RAG 2 is creation of a nick at the heptamer / coding flank border . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
In vitro coding joint formation requires RAG 1 , RAG 2 , and heat labile factors present in the nuclear extract of nonlymphoid cells . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 dependent assembly of functional complexes with 5 ( D ) J recombination substrates in solution . 5 ( D ) J recombination is initiated by RAG 1 and RAG 2 , which introduce double strand DNA breaks at recombination signal sequences ( RSSs ) of antigen receptor gene segments to produce signal ends , terminating in blunt , double strand breaks , and coding ends , terminating in DNA hairpins . ^^^ While the formation of RAG RSS complexes has been documented , observations regarding the individual contributions of RAG 1 and RAG 2 to RSS recognition are in conflict . ^^^ Notably , the presence of both RAG 1 and RAG 2 is essential for formation of stable , functional complexes with substrate DNA under conditions of the sequestration assay . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Hence , it became obvious that the initial steps of the reaction are carried out by the lymphocyte specific proteins RAG 1 and RAG 2 ( recombination activating genes ) , with the help of members of the high mobility group protein family of DNA binding proteins , HMG 1 or HMG 2 . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Cloning and characterization of the human recombination activating gene 1 ( RAG 1 ) and RAG 2 promoter regions . ^^^ Recombination activating gene 1 ( RAG 1 ) and RAG 2 are the essential and tissue specific components of 5 ( D ) J recombination . ^^^ We have characterized the genomic organization of the human RAG locus , mapped the transcriptional initiation sites , and partially sequenced and performed functional reporter assays on the 5 ' flanking regions of human RAG 1 and RAG 2 . ^^^ The 5 ' flanking region of the human RAG 2 gene is TATA less ; however , there is a GATAA consensus at position 34 with respect to the major transcriptional initiation site of RAG 1 . ^^^ Promoter regions of human RAG 1 and RAG 2 are active in both lymphoid and nonlymphoid cell lines , suggesting that an outside regulatory element is probably involved in the tissue specific transcriptional regulation of the RAG genes . . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Rag 1 and Rag 2 are required for the somatic rearrangement of immunoglobulin genes and T cell receptor genes and the subsequent development of B and T cells . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
To examine whether the development of thymic lymphoma in p 53 / mice was dependent on the process of 5 ( D ) J recombination , we generated p 53 / mice that were also mutant for the Rag 1 or Rag 2 genes . ^^^ Both Rag 1 / ; p 53 / and Rag 2 / ; p 53 / mice developed thymic lymphoma at high frequency , and the tumors arose with short latency . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Rejoining of DNA by the RAG 1 and RAG 2 proteins . ^^^ Assembly of immunoglobulin and T cell receptor genes from separate gene segments [ 5 ( D ) J recombination ] begins with DNA double strand breakage by the RAG 1 and RAG 2 proteins , acting at a pair of recombination signal sequences ( RSSs ) . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
To investigate potential roles of the RAG 1 and RAG 2 gene products in Ig heavy chain class recombination ( CSR ) , we have generated RAG 1 ( / ) and RAG 2 ( / ) mice which contain both a rearranged Ig HC 5 ( D ) J gene ( referred to as B 1 8 ) inserted into the endogenous Ig heavy chain ( HC ) locus in place of the JH segments , and a rearranged lambda 1 light chain ( LC ) transgene ( which are referred to as RAG 1 ( / ) B 1 8lambda and RAG 2 ( / ) B 1 8lambda mice respectively ) . ^^^ The B 1 8 HC gene and lambda LC genes encode proteins that associate to form a complete Ig molecule , the expression of which leads to substantial reconstitution of the peripheral B cell compartments of RAG 1 ( / ) B 1 8lambda and RAG 2 ( / ) B 1 8lambda mice . ^^^ Both RAG 1 ( / ) B 1 8lambda and RAG 2 ( / ) B 1 8lambda mice have relatively normal levels of the various IgG isotypes , but greatly reduced levels of serum IgM and IgA compared to normal littermates . ^^^ Furthermore , RAG 1 ( / ) B 1 8lambda and RAG 2 ( / ) B 1 8lambda B cells activated in vitro with lipopolysaccharide ( LPS ) or LPS plus IL 4 responded similarly to control B cells with respect to surface expression and secretion of IgG 3 , IgG 1 , IgG2b , IgG2a and IgE , but again were deficient in the secretion of IgM . ^^^ Together , these findings indicate that neither RAG 1 nor RAG 2 expression is required for efficient class switching to most HC isotypes in B cells . . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Recombination activating gene ( RAG ) deficiencies were introduced into both p 53 / mice and TgTDeltaN transgenic mice , a strain in which 100 % of the mice develop thymoma due to thymocyte specific inactivation of p 53 by a simian virus 40 T antigen variant . 5 ( D ) J recombination was dispensable for tumorigenesis since thymomas developed with or without the RAG 1 or RAG 2 gene , although some delay was observed . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Inspection of the 3 ' UTR genomic region for RAG 1 and RAG 2 in rainbow trout ( Oncorhynchus mykiss ) reveals potential regulatory motifs . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Lack of expression of the recombination activating genes RAG 1 and RAG 2 in cutaneous T cell lymphoma : pathogenic implications . ^^^ To study whether illegitimate 5 ( D ) J recombination is responsible for the continuously increasing number of DNA breaks in CTCL , we used reverse transcriptase polymerase chain reaction ( RT PCR ) to analyse three CTCL cell lines and biopsies from 14 CTCL patients for the expression of the RAG 1 and RAG 2 genes which are essential for 5 ( D ) J recombination . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
In contrast to 5 ( D ) J recombination , which is mediated by RAG 1 , RAG 2 and DNA double stranded break ( DSB ) repair proteins , little is known about the mechanism of switching . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RT PCR revealed that TCDD reduced RAG 1 , RAG 2 , and TdT gene expression in the CD 4 CD8 double negative thymocytes . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The site specific recombination of antigen receptor gene segments in T and B lymphocytes is dependent on the expression of two recombination activating genes , RAG 1 and RAG 2 . ^^^ The RAG 1 and RAG 2 proteins are essential for the cleavage of DNA at highly conserved recombination signals to make double strand breaks and their expression is sufficient to confer 5 ( D ) J recombination activity to non lymphoid cells . ^^^ However , several laboratories have now demonstrated expression of RAG 1 and RAG 2 and active 5 to ( D ) J recombination in germinal center B cells . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Expression of CD 3 epsilon , CD 3 zeta , and RAG 1 / RAG 2 in decidual CD56+ NK cells . ^^^ In contrast to previous reports , there was no evidence of RAG 1 nor RAG 2 expression in decidual NK cells . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
In the studies reported here , the authors have analysed cytokine / growth factor gene expression , recombinase activating gene RAG 1 and RAG 2 gene expression and terminal deoxynucleotidyl transferase ( TdT ) gene expression in mouse fetal intestine and fetal thymus and liver , two known haematopoietic tissues . ^^^ RAG 1 and RAG 2 mRNA was detected in all three fetal tissues . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Genomic rearrangement of the antigen receptor loci is initiated by the two lymphoid specific proteins Rag 1 and Rag 2 . ^^^ We report here that patients with Omenn syndrome , a severe immunodeficiency characterized by the presence of activated , anergic , oligoclonal T cells , hypereosinophilia , and high IgE levels , bear missense mutations in either the Rag 1 or Rag 2 genes that result in partial activity of the two proteins . ^^^ Two of the amino acid substitutions map within the Rag 1 homeodomain and decrease DNA binding activity , while three others lower the efficiency of Rag 1 / Rag 2 interaction . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
This process is initiated by the recombination activating proteins RAG 1 and RAG 2 , which recognize the recombination signal sequences ( RSS ) and cleave the DNA at the coding / RSS junction . ^^^ In this study , we show that RAG 1 and RAG 2 have the ability to directly interact in solution before binding to the DNA . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Recombination activating genes , RAG 1 and RAG 2 , encode proteins that catalyze the rearrangement of immunoglobulin genes in B cells and T cell receptor genes in T cells to generate the diversity of these important recognition molecules in immune system . ^^^ However , recent studies have revealed that even mature B cells in peripheral lymphoid tissues can reexpress RAG 1 and RAG 2 proteins following immunization . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The adult thymus has multiple defects , including reduced cell numbers and proportions of the more mature thymocyte subsets , a complete absence of CD25+ cells and a reduced level of RAG 1 and RAG 2 expression . ^^^ Moreover , normal levels of RAG 1 and RAG 2 were observed . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The RAG 1 and RAG 2 proteins , as well as the DNA bending protein HMG 1 , are needed for efficient formation of this complex . ^^^ After cleavage , all four broken DNA ends remain associated with the RAG proteins in a postcleavage synaptic complex , whose existence helps to explain the known role of RAG 1 and RAG 2 in the subsequent end joining events that complete 5 ( D ) J recombination . . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Distinct roles of RAG 1 and RAG 2 in binding the 5 ( D ) J recombination signal sequences . ^^^ The RAG 1 and RAG 2 proteins initiate 5 ( D ) J recombination by introducing double strand breaks at the border between a recombination signal sequence ( RSS ) and a coding segment . ^^^ To understand the distinct functions of RAG 1 and RAG 2 in signal recognition , we have compared the DNA binding activities of RAG 1 alone and RAG 1 plus RAG 2 by gel retardation and footprinting analyses . ^^^ Although direct binding of RAG 2 by itself was not detected , the presence of both RAG 1 and RAG 2 results in the formation of a RAG 1 RAG2 DNA complex which is more stable and more specific than the RAG 1 DNA complex and is active in 5 ( D ) J cleavage . ^^^ These results suggest that biologically effective discrimination between an RSS and nonspecific sequences requires both RAG 1 and RAG 2 . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Cleavage in vitro by the RAG 1 and RAG 2 proteins can occur at individual signals when the reaction buffer contains Mn2+ , but cleavage is restricted to substrates containing two signals when Mg2+ is the divalent cation . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Rag 1 and Rag 2 are the critical components of the 5 ( D ) J recombinase required for site specific recombination of the antigen receptor genes . ^^^ In this study , we have examined the ability of recombinant ( r ) Rag 1 and Rag 2 to bind the recombination signal sequences ( RSS ) and have determined that rRag 1 , but not rRag 2 , is able to directly bind DNA . rRAG 1 DNA binding activity was found to reside within a novel amino terminal arginine rich ( RR ) domain with partial homology to a variety of nucleic acid binding domains . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Recombination is initiated by the RAG 1 and RAG 2 proteins , which introduce double stranded DNA breaks ( DSB ) adjacent to the Ig and TCR gene segments . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
V ( D ) J recombination signal recognition : distinct , overlapping DNA protein contacts in complexes containing RAG 1 with and without RAG 2 . ^^^ Protein interactions with 5 ( D ) J recombination signal sequences ( RSSs ) were mapped in complexes containing RAG 1 with ( M1 / 2 ) or without ( M 1 ) RAG 2 . ^^^ Thus , while RAG 1 alone can bind the nonamer , RAG 2 is required for heptamer occupancy . . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Because a common 5 ( D ) J recombinase comprising RAG 1 and RAG 2 proteins is used for both B and T cell antigen receptor assembly , lineage specific rearrangement must be modulated through differential access to sites of recombination . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Transposition mediated by RAG 1 and RAG 2 and its implications for the evolution of the immune system . ^^^ The proteins encoded by the recombination activating genes , RAG 1 and RAG 2 , are essential in this reaction , mediating sequence specific DNA recognition of well defined recombination signals and DNA cleavage next to these signals . ^^^ Here we show that RAG 1 and RAG 2 together form a transposase capable of excising a piece of DNA containing recombination signals from a donor site and inserting it into a target DNA molecule . ^^^ The results support the theory that RAG 1 and RAG 2 were once components of a transposable element , and that the split nature of immunoglobulin and T cell receptor genes derives from germline insertion of this element into an ancestral receptor gene soon after the evolutionary divergence of jawed and jawless vertebrates . . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
DNA transposition by the RAG 1 and RAG 2 proteins : a possible source of oncogenic translocations . ^^^ The RAG 1 and RAG 2 proteins are known to initiate 5 ( D ) J recombination by making a double strand break between the recombination signal sequence ( RSS ) and the neighboring coding DNA . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The RAG 1 and RAG 2 proteins play a crucial role in 5 ( D ) J recombination by cooperating to make specific double stranded DNA breaks at a pair of recombination signal sequences ( RSSs ) . ^^^ Given the known properties of the beta propeller fold in mediating protein protein interactions , it is proposed that this six laded propeller structure of the RAG 2 active core would play a crucial role in the tight complex formed by the RAG 1 and RAG 2 proteins and RSSs . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Under physiologic conditions , we found that the complex of RAG 1 , RAG 2 , and HMG 1 can successfully recapitulate the 12 / 23 rule with the same specificity as that seen intracellularly and in crude extracts . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Re expression of RAG 1 and RAG 2 genes and evidence for secondary rearrangements in human germinal center B lymphocytes . 5 ( D ) J recombination occurs in immature B cells within primary lymphoid organs . ^^^ However , recent evidence demonstrated that the recombination activating genes RAG 1 and RAG 2 can also be expressed in murine germinal centers ( GC ) where they can mediate secondary rearrangements . ^^^ In the present report , we provide evidence that human GC B cells that have lost surface immunoglobulin re express RAG 1 and RAG 2 , suggesting that they may be able to undergo Ig rearrangement . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Checkpoints in thymocytopoiesis in aging : expression of the recombination activating genes RAG 1 and RAG 2 . ^^^ We examined the expression of recombinase activating genes , RAG 1 and RAG 2 , in the thymus of mice at different ages ( 2 24 months ) . ^^^ A significant age related decrease in RAG 1 and RAG 2 expression was observed in the thymocytes from the age of 12 months and over . ^^^ Whereas cells derived from the immature thymocytes of the old donors failed to express RAG 1 and RAG 2 , compared to the young , the bone marrow derived cells of both age groups did show this expression , and there was no difference in Vbeta rearrangement of the TCR . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Both B 220 ( ) and B 220 ( + ) cells similarly express the IgH germ line transcript ( Imu ) , mRNAs for recombinase ( TdT , Rag 1 , and Rag 2 ) , and lymphoid specific transcription factors ( Pax 5 , EBF , E12 / E47 , Oct 2 , and Ikaros ) , but the DNA binding activity of Pax 5 , EBF , Oct 2 , and E2A are low in B 220 ( ) cells and while high in B 220 ( + ) cells . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 cooperate in specific binding to the recombination signal sequence in vitro . ^^^ This process , termed `` 5 ( D ) J recombination , ' ' begins with DNA cleavage at the appropriate sites mediated by the two proteins RAG 1 and RAG 2 . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The recombination activating genes RAG 1 and RAG 2 are expressed in a lymphoid cell specific and developmentally regulated fashion . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Peripheral CD4+ T cells reexpress the recombination activating genes , RAG 1 and RAG 2 , and contain signal end intermediates indicative of ongoing 5 ( D ) J recombination . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Sequence of the rag 1 and rag 2 intergenic region in zebrafish ( Danio rerio ) . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The recombination activating genes RAG 1 and RAG 2 are highly conserved throughout evolution and are necessary and essential for the DNA rearrangement of antigen receptor gene segments . ^^^ Experiments with a mouse fibroblast line stably transfected with a genomic fragment of the RAG locus suggest that the intergenic region between RAG 1 and RAG 2 may contain information modulating RAG transcription . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
In striking contrast to the plasma cell phenotype , recombination activating genes , RAG 1 and RAG 2 , were expressed in the HTD 8 cells and were shown to be necessary , but insufficient for inducing expression of the new lambda chain . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Similar to the effects of an immunoglobulin ( Ig ) mu heavy chain ( HC ) transgene , activated Ras caused progression of RAG 1 deficient progenitor ( pro ) B cells to cells that shared many characteristics with precursor ( pre ) B cells , including downregulation of surface CD 43 expression plus expression of lambda 5 , RAG 2 , and germline kappa locus transcripts . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Hairpin coding end opening is mediated by RAG 1 and RAG 2 proteins . ^^^ Here , we show that RAG 1 plus RAG 2 can open DNA hairpins . ^^^ Mutations in either RAG 1 or RAG 2 that interfere with RSS cleavage also interfere with hairpin opening , suggesting that RAGs have a single active site that catalyzes several distinct DNA cleavage reactions . . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Here we show that B 1 cells , like germinal centre B cells , can express recombinase activating genes 1 and 2 ( RAG 1 and RAG 2 ) and undergo secondary 5 ( D ) J recombination of immunoglobulin genes . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Roles of the `` dispensable ' ' portions of RAG 1 and RAG 2 in 5 ( D ) J recombination . 5 ( D ) J recombination is initiated by introduction of site specific double stranded DNA breaks by the RAG 1 and RAG 2 proteins . ^^^ It is not known whether truncating RAG 1 and / or RAG 2 affects the cleavage step or the joining step of recombination . ^^^ Furthermore , we found that removal of portions of the dispensable regions of RAG 1 and RAG 2 affects the efficiency of product formation without altering the levels of recombination intermediates . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 2 promotes heptamer occupancy by RAG 1 in the assembly of a 5 ( D ) J initiation complex . 5 ( D ) J recombination occurs at recombination signal sequences ( RSSs ) containing conserved heptamer and nonamer elements . ^^^ RAG 1 and RAG 2 initiate recombination by cleaving DNA between heptamers and antigen receptor coding segments . ^^^ RAG 2 by itself has no DNA binding activity but promotes heptamer occupancy in the presence of RAG 1 ; how RAG 2 collaborates with RAG 1 has been poorly understood . ^^^ Here we examine the composition of RAG RSS complexes and the relative contributions of RAG 1 and RAG 2 to heptamer binding . ^^^ RAG 1 exists as a dimer in complexes with an isolated RSS bearing a 12 bp spacer , regardless of whether RAG 2 is present ; only a single subunit of RAG 1 , however , participates in nonamer binding . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
DNA cleavage is mediated by the RAG 1 and RAG 2 proteins . ^^^ We also detect cross linking of RAG 2 protein to some of the same nucleotides that cross link to RAG 1 , indicating that , in the binding complex , both RAG proteins are in close proximity to the site of cleavage . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Omenn syndrome : a disorder of Rag 1 and Rag 2 genes . ^^^ This process , known as 5 ( D ) J recombination , is initiated by the lymphoid specific proteins Rag 1 and Rag 2 . ^^^ Both in humans and in animal models , mutations that abrogate expression of either the Rag 1 or Rag 2 proteins result in severe combined immune deficiency with a complete lack of circulating T and B cells due to an early block in lymphoid development . ^^^ We have recently shown that mutations that impair , but do not completely abolish the function of Rag 1 and Rag 2 in humans result in Omenn syndrome , an enigmatic form of combined immune deficiency characterized by oligoclonal , activated T lymphocytes with a skewed Th 2 profile . . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
DNA hairpin opening mediated by the RAG 1 and RAG 2 proteins . ^^^ The lymphoid cell specific proteins RAG 1 and RAG 2 initiate 5 ( D ) J recombination by cleaving DNA adjacent to recombination signals , generating blunt signal ends and covalently sealed , hairpin coding ends . ^^^ Here we demonstrate that RAG 1 and RAG 2 possess an intrinsic single stranded nuclease activity capable of nicking hairpin coding ends at or near the hairpin tip . ^^^ RAG 1 and RAG 2 may therefore be responsible for initiating the processing of coding ends and for the generation of P nucleotides during 5 ( D ) J recombination . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
A RAG 1 and RAG 2 tetramer complex is active in cleavage in 5 ( D ) J recombination . ^^^ During 5 ( D ) J recombination two proteins , RAG 1 and RAG 2 , assemble as a protein DNA complex with the appropriate DNA targets containing recombination signal sequences ( RSSs ) . ^^^ The coexpressed RAG 1 and RAG 2 proteins form a mixed tetramer in solution which contains two molecules of each protein . ^^^ The same tetramer of RAG 1 and RAG 2 plus one DNA molecule is the form active in cleavage . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 are the two lymphoid specific proteins required for the cleavage of DNA sequences known as the recombination signal sequences ( RSSs ) flanking 5 , D or J regions of the antigen binding genes . ^^^ Previous studies have shown that RAG 1 alone is capable of binding to the RSS , whereas RAG 2 only binds as a RAG1 / RAG2 complex . ^^^ We have expressed recombinant core RAG 1 ( amino acids 384 1008 ) in Escherichia coli and demonstrated catalytic activity when combined with RAG 2 . ^^^ The purified RAG 1 protein overexpressed in E . coli exhibited the expected cleavage activity when combined with RAG 2 purified from transfected 293T cells . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
In this report , we investigated the basis of this regulation by testing the ability of purified RAG 1 and RAG 2 proteins to initiate cleavage on positioned nucleosomes containing RSS substrates . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
HB4C5 is a human antibody producing plasma B cell line that expresses the recombination activating gene 1 ( RAG 1 ) and RAG 2 constitutively , but undergoes few secondary immunoglobulin gene rearrangements when cultured in fetal bovine serum containing medium . ^^^ To investigate the induction mechanism of secondary VlambdaJlambda rearrangement , we assessed the expression levels of RAG 1 and RAG 2 products , Vlambda germline transcription level and the amount of Vlambda signal broken ends ( SBE ) in HB4C5 cells cultured in serum supplemented or serum free medium . ^^^ Western blot analysis showed that the expression level for the RAG 1 and RAG 2 proteins was not affected by the serum depletion . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The steady state level of both RAG 1 and RAG 2 mRNA , the number of Pre B cells , and the number of Pre B cells expressing RAG 2 protein decrease in the bone marrow of old mice . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Pro B cells from Ebf+ / E2a+ / mice show reduced expression of lymphoid specific transcripts , including Pax 5 , Rag 1 , Rag 2 , and mb 1 . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Coordinate regulation of RAG 1 and RAG 2 by cell type specific DNA elements 5 ' of RAG 2 . ^^^ RAG 1 and RAG 2 are essential for 5 ( D ) J recombination and lymphocyte development . ^^^ The regulation of RAG 1 and RAG 2 was investigated in vivo with bacterial artificial chromosome ( BAC ) transgenes containing a fluorescent indicator . ^^^ Coordinate expression of RAG 1 and RAG 2 in B and T cells was found to be regulated by distinct genetic elements found on the 5 ' side of the RAG 2 gene . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 proteins cleave precisely at the RSS coding sequence border leading to flush signal ends and coding ends with a hairpin structure ( Eastman , M . , Leu , T . , Schatz , D . , 1996 . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Transposition mediated by RAG 1 and RAG 2 and the evolution of the adaptive immune system . ^^^ The RAG 1 and RAG 2 proteins together initiate 5 ( D ) J recombination by performing cleavage of chromosomal DNA adjacent to antigen receptor gene segments . ^^^ Like the adaptive immune system itself , RAG 1 and RAG 2 are found only in jawed vertebrates . ^^^ The hypothesis that RAG 1 and RAG 2 arose in evolution as components of a transposable element has received dramatic support from our recent finding that the RAG proteins are a fully functional transposase in vitro . ^^^ This result strongly suggests that antigen receptor genes acquired their unusual structure as a consequence of the insertion of a transposable element into an ancestral receptor gene by RAG 1 and RAG 2 approx 450 million years ago . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Moreover , the expression of genes encoding components of the rearrangement machinery ( RAG 1 , RAG 2 , TdT ) or pre B cell receptor ( lambda 5 , VpreB , Igalpha , Igbeta ) has been considered to indicate B lineage commitment . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The 5 ( D ) J recombination reaction is directed by a recombinase complex from the RAG 1 and RAG 2 genes , and is modulated by several other gene products . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
We addressed whether this was related to their immunodeficiency by similarly treating Rag 1 ( / ) and Rag 2 ( / ) knockout mice which also lack mature T and B lymphocytes . ^^^ |
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Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Mutational analysis of RAG 1 and RAG 2 identifies three catalytic amino acids in RAG 1 critical for both cleavage steps of 5 ( D ) J recombination . ^^^ RAG 1 and RAG 2 initiate 5 ( D ) J recombination , the process of rearranging the antigen binding domain of immunoglobulins and T cell receptors , by introducing site specific double strand breaks ( DSB ) in chromosomal DNA during lymphocyte development . ^^^ We altered each conserved acidic amino acid in RAG 1 and RAG 2 by site directed mutagenesis , and examined > 100 mutants using a combination of in vivo and in vitro analyses . ^^^ No conserved acidic amino acids in RAG 2 were critical for catalysis ; three RAG 1 mutants retained normal DNA binding , but were catalytically inactive for both nicking and hairpin formation . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The RAG 1 and RAG 2 proteins collaborate to initiate 5 ( D ) J recombination by binding recombination signal sequences ( RSSs ) and making a double strand break between the RSS and adjacent coding DNA . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Some mutations that alter the amino acid sequence of RAG 1 or RAG 2 have been shown to disturb B cell generation and to partially disturb T cell generation , resulting in Omenn syndrome in humans ; moreover , peripheral re expression of RAGs indicates their role in lymphoid cell homeostasis . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
We have previously identified a DDE like region in the RAG 2 protein and a similar region within the RAG 1 protein . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
In contrast , the generation of pre pro B cells and pro B cells appeared to be normal , as judged by total cell numbers , proliferative indexes , D JH and 5 DJH gene rearrangements , and mRNA for recombinase activating gene 1 ( RAG 1 ) , RAG 2 , TdT , Ig mu , lambda 5 , and VpreB . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
In addition to RAG 1 and RAG 2 , the protein HMG 1 is known to stimulate the efficiency of the cleavage reaction . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
During 5 ( D ) J recombination , the RAG 1 and RAG 2 proteins cooperate to catalyze a series of DNA bond breakage and strand transfer reactions . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Although the plasma cells used express both RAG 1 and RAG 2 , the expression level of these proteins was not affected by caffeine or okadaic acid . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The process of antigen receptor gene rearrangement , 5 ( D ) J recombination , involves DNA cleavage by the RAG 1 and RAG 2 proteins . ^^^ To test this hypothesis , we constructed mutant versions of RAG 1 and RAG 2 in which all four DNA PK consensus phosphorylation sites were removed by site directed mutagenesis . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Mutations were detected in the probands as well as in their parents by genomic sequencing of the complete coding regions of both RAG 1 and RAG 2 , which are contained in a single exon . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The recombinase activating genes , RAG 1 and RAG 2 , can be expressed by a subset of B cells within germinal centers , where they mediate secondary 5 ( D ) J rearrangements . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Omenn syndrome was recently found to be caused by missense mutations in RAG 1 or RAG 2 gene that result in partial 5 ( D ) J recombination activity . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The recombinase activating genes ( RAG 1 and RAG 2 ) encode nuclear proteins that directly mediate the mechanism 5 ( D ) J recombination process that occurs in T and B lymphocytes . ^^^ The expression of RAG 1 and RAG 2 is required for the proper development of maturing lymphocytes . ^^^ We found three complete genes , RAG 1 , RAG 2 and ACS ( a possible homologue of the plant 1 aminocyclopropane carboxylate synthase gene ) . ^^^ The genetic structure of both RAG 1 and RAG 2 is identical to that found in other fish , but the size of the intergenic region is smaller in Fugu . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Here we report that the high mobility group protein , HMG 1 , is necessary for the correct nicking of the 23 bp recombination signal sequence ( 23 RSS ) by the recombination [ corrected ] activating gene ( RAG ) proteins , RAG 1 and RAG 2 . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
A common recombination mechanism , initiated by the proteins RAG 1 and RAG 2 at conserved recombination signal sequences ( RSSs ) , operates at all rearranging loci [ 2 ] [ 3 ] . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
In this report , we use deletion mapping and site directed mutagenesis to determine the minimal domains critical for interaction between RAG 1 and RAG 2 . ^^^ We define the active core of RAG 2 required for RSS cleavage as aa 1 371 and demonstrate that the C terminal 57 aa of this core provide a dominant surface for RAG 1 interaction . ^^^ We also show that zinc finger B ( aa 727 750 ) of RAG 1 provides a dominant interaction domain for recruiting RAG 2 . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The RAG proteins and 5 ( D ) J recombination : complexes , ends , and transposition . 5 ( D ) J recombination proceeds through a series of protein : DNA complexes mediated in part by the RAG 1 and RAG 2 proteins . ^^^ Finally , we discuss the evolutionary and functional implications of the finding that RAG 1 and RAG 2 constitute a transposase , and we consider RAG protein biochemistry in the context of several bacterial transposition systems . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Recombination activating gene 1 ( RAG 1 ) and RAG 2 are expressed in lymphoid cells undergoing the antigen receptor gene rearrangement . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Here we show that E2A proteins act in concert with RAG 1 and RAG 2 to activate Ig VK1J but not Iglambda VlambdaIII Jlambda 1 rearrangement in an embryonic kidney cell line . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The proteins encoded by RAG 1 and RAG 2 can initiate gene recombination by site specific cleavage of DNA in immunoglobulin and T cell receptor ( TCR ) loci . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The site specific cleavage mediated by RAG 1 and RAG 2 proteins generates two types of double strand DNA breaks : blunt signal ends and covalently sealed hairpin coding ends . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Two lymphoid specific proteins , RAG 1 and RAG 2 , initiate this process at two recombination signal sequences . ^^^ RAG 1 possesses the active site of the 5 ( D ) J recombinase although RAG 2 is essential for signal binding and cleavage . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Recombination activating genes RAG 1 and RAG 2 are essential components of 5 ( D ) J recombination , a process that generates the specific antigen receptors in lymphocytes . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 expression by B cell subsets from human tonsil and peripheral blood . ^^^ Neither RAG 1 nor RAG 2 mRNA was routinely found in normal peripheral blood B cells . ^^^ In individual tonsil B cells , RAG 1 and RAG 2 mRNAs were found in 18 % of naive B cells , 22 % of GC founder cells , 0 % of centroblasts , 13 % of centrocytes , and 9 % of memory B cells . ^^^ Individual naive tonsil B cells containing both RAG 1 and RAG 2 mRNA were activated ( CD 69 ( + ) ) . ^^^ In normal peripheral blood approximately 5 % of B cells expressed both RAG 1 and RAG 2 . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
However , the expression of a heterogeneous ( T + NK or myeloid ) marker profile or of `` early ' ' antigens ( such as TdT , CD 10 , RAG 1 , RAG 2 ) render them more likely to be in the acute leukemia group . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Furthermore , we show that the lymphocyte specific endonuclease encoded by the recombinase activating genes ( RAG 1 and RAG 2 ) is required for radiation induced thymic lymphomagenesis in SCID mice . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
DNA cleavage is catalyzed by RAG 1 and RAG 2 in two chemical steps : first strand nicking , followed by hairpin formation via direct transesterification . ^^^ In vitro , these reactions minimally proceed in discrete protein DNA complexes containing dimeric RAG 1 and one or two RAG 2 monomers bound to a single recombination signal sequence . ^^^ To investigate which RAG 1 subunit contributes the residues of the DDE triad to the recombinase active site , cleavage of intact or prenicked DNA substrates was analyzed in situ in complexes containing RAG 2 and a RAG 1 heterodimer that carried an active site mutation targeted to the same or opposite RAG 1 subunit mutated to be incompetent for DNA binding . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Expression of T cell receptor and surface immunoglobulins on T and B lymphocytes , respectively , is strictly dependent on the variable , ( diversity ) joining exon ( 5 ( D ) J ) recombination process , which is initiated by the lymphoid specific recombinase activating gene proteins 1 and 2 ( RAG 1 and RAG 2 ) . ^^^ Recent advances have highlighted the functional organization of the RAG 1 and RAG 2 proteins and have provided important information on the regulation of RAG gene expression . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The only established physiological function of the 5 ( D ) J recombinase , comprising RAG 1 and RAG 2 , is to perform DNA cleavage . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Missense mutations detected in OS have been examined in a number of biochemical assays and have contributed to dissect the various functional domains of both Rag 1 and Rag 2 proteins . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Our results demonstrate that DMSO induces cell growth inhibition , cell phenotype changes , with down regulation of CD 2 and CD 7 , and increases in alpha / beta or gamma / delta TCR chains led by TdT , RAG 1 and RAG 2 activity . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Central to this reaction is the organization of the protein DNA complex containing the proteins RAG 1 and RAG 2 and their DNA targets . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Two proteins , RAG 1 and RAG 2 , together form the nuclease that cleaves the DNA at the border of the signal sequences . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Expression of the recombination activating genes ( RAG 1 and RAG 2 ) is not detectable in Epstein Barr virus associated human lymphomas . ^^^ The expression of the recombination activating genes ( RAG 1 and RAG 2 ) is largely restricted to immature lymphoid cells . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
It has been hypothesized that OR gene regulation may involve stochastic DNA rearrangement , which in lymphocytes requires the recombination activating genes , rag 1 and rag 2 . ^^^ Here we report that rag 2 , the obligate partner for rag 1 function , is also expressed in OSNs and that its expression pattern mimics that of rag 1 . ^^^ The onset of rag 1 and rag 2 expression preceded that of known zebrafish ORs and the number of rag 1 positive OSNs corresponded with the number expressing the olfactory cyclic nucleotide gated cation channel , an OSN marker . ^^^ The expression of rag 1 and rag 2 in OSNs adds to the list of similarities between the olfactory and immune systems that includes monoallelic and mutually exclusive gene expression . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Identical mutations in RAG 1 or RAG 2 genes leading to defective 5 ( D ) J recombinase activity can cause either T B severe combined immune deficiency or Omenn syndrome . ^^^ Inherited mutations in either the recombination activating genes RAG 1 or RAG 2 , resulting in partial 5 ( D ) J recombinase activity , were shown to be responsible for OS . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 in 5 ( D ) J recombination and transposition . ^^^ RAG 1 and RAG 2 are the key components of the 5 ( D ) J recombinase machinery that catalyses the somatic gene rearrangements of antigen receptor genes during lymphocyte development . ^^^ The individual roles of RAG 1 and RAG 2 in 5 ( D ) J recombination and transposition reactions are discussed based on mutation analyses and structure predictions . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Another SCID , RAG 1 and RAG 2 recombinase deficiency , may produce a typical form with a characteristic T B NK + phenotype , Omenn ' s syndrome , or forms with an unexpected T B + NK + phenotype . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Identification of two topologically independent domains in RAG 1 and their role in macromolecular interactions relevant to 5 ( D ) J recombination . 5 ( D ) J recombination is instigated by the recombination activating proteins RAG 1 and RAG 2 , which catalyze site specific DNA cleavage at the border of the recombination signal sequence ( RSS ) . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
To examine the physiologic role of the second wave of RAG expression , we analyzed mice that can not reinduce RAG expression in CD 4 ( + ) CD 8 ( + ) T cells because the transgenic locus that directs RAG 1 and RAG 2 expression in these mice is missing a distal regulatory element essential for reinduction . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Mutations of the RAG 1 or RAG 2 protein that eliminate their recombination activity result in T B severe combined immunodeficiency ( SCID ) , whereas mutations retaining partial recombination activity lead to Omenn syndrome , a peculiar SCID characterized by increased host T cells and absence of circulating B cells . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Careful assessment of proliferation ( Ki 67 ) and apoptosis ( terminal dUTP nick end labeling ) indicators and of the occurrence of secondary immunoglobulin gene rearrangements ( RAG 1 and RAG 2 ) confirmed the parallelism . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Investigated was whether cotransfection of RAG 1 and RAG 2 genes in combination with lymphoid transcription factors can induce TCR gene rearrangements in nonlymphoid human cells . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Identification of basic residues in RAG 2 critical for DNA binding by the RAG 1 RAG2 complex . ^^^ In 5 ( D ) J recombination , the RAG 1 and RAG 2 proteins are the essential components of the complex that catalyzes DNA cleavage . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Somatic 5 ( D ) J recombination of the immune receptor genes is mediated by the recombination signal sequence ( RSS ) and the recombination activating genes RAG 1 and RAG 2 . ^^^ Notably , its affinity for the RSS decreased when RAG 1 and RAG 2 were induced . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
All 39 5 ( H ) elements ( with their adjacent heptamer / nonamer signal ) were tested for site specific cleavage with purified human core RAG 1 and RAG 2 , and HMG 1 proteins in a 12 / 23 coupled cleavage reaction . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
This complex , composed of a dimer of RAG 2 and at least a trimer of RAG 1 , remains inactive for double strand break formation until a second complementary signal is provided . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
We showed that Rag 1 ( C57BL / 6 background ) and Rag 2 ( BALB / c background ) knockout mice , which lack both T and B cells , chronically shed high levels of rotavirus Ag in stool samples following oral inoculation . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Early death and severe lymphopenia caused by ubiquitous expression of the Rag 1 and Rag 2 genes in mice . ^^^ The recombination activating proteins ( RAG 1 and RAG 2 ) are essential for 5 ( D ) J recombination of immunoglobulin chains . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 ( RAGs ) initiate 5 ( D ) J recombination by introducing breaks between two coding segments and flanking recombination signals ( RSs ) . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Expression of the recombination activating genes in extrafollicular lymphocytes but no apparent reinduction in germinal center reactions in human tonsils . 5 ( D ) J recombination in lymphocytes is mediated by 2 recombination activating genes , RAG 1 and RAG 2 , which are expressed during lymphocyte development in bone marrow and thymus . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The recombination activating gene 1 ( RAG 1 ) and RAG 2 are expressed specifically in immature lymphoid cells undergoing the recombination of antigen receptor genes . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Two lymphoid cell specific proteins , RAG 1 and RAG 2 , initiate 5 ( D ) J recombination by introducing DNA breaks at recombination signal sequences ( RSSs ) . ^^^ In contrast , 23 RSS complexes containing both RAG proteins and either HMG 1 or HMG 2 exhibited enhanced cleavage activity and displayed an altered distribution of cleavage products compared to 23 RSS complexes containing only RAG 1 and RAG 2 . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
PU . 1 expression can downregulate pre Talpha , Rag 1 , and Rag 2 in a dose dependent manner , and higher PU . 1 levels induce Mac 1 and Id 2 . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
In the other one , the DSB is made by the RAG 1 and RAG 2 proteins . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
These defects are attenuated in vivo , but bone marrow B cells display an unusual pattern of cell surface marker expression and show decreased transcript levels for TdT , Rag 1 , Rag 2 and lambda 5 . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
These cells had reduced expression of the recombinase activating genes , RAG 1 and RAG 2 . ^^^ Their receptor negative pre B cell progeny were relatively small , expressed RAG 1 and RAG 2 , and exhibited selective down regulation of VpreB and lambda 5 expression . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
A portion of these SCID patients bear a defect in either of the two recombination activating genes , Rag 1 or Rag 2 , while others have mutations in a newly identified gene , Artemis . ^^^ Omenn syndrome is an unusual severe immunodeficiency with T cells but no B cells , and peculiar features also due to a defect in Rag 1 or Rag 2 genes . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
To test the possibility that RAG 1 and RAG 2 differ in their roles in tumorigenesis , we studied Rag 1 ( / ) Atm ( / ) mice in parallel to our previous Rag 2 ( / ) Atm ( / ) study . ^^^ We found that thymic lymphomas occur at high frequency in Rag 1 ( / ) Atm ( / ) mice and resemble those that occur in Rag 2 ( / ) Atm ( / ) mice . ^^^ These results indicate that both RAG 1 and RAG 2 are necessary for tumorigenesis involving translocation in the Tcr alpha / delta locus but that Atm deficiency leads to tumors through a broader RAG independent predisposition to translocation , related to a generalized defect in dsDNA break repair . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Although both RAG 1 and RAG 2 are required for all steps of 5 ( D ) J recombination , little is known about the specific contribution of either protein to these steps . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
In genetic engineered B cells stably transfected with inducible expression vectors for the recombination activating genes RAG 1 , RAG 2 , or both , the avidity of KRC to DNA was markedly decreased when RAG 1 and RAG 2 were overexpressed . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Both transcription factors can interfere with expression of the Rag 1 and Rag 2 recombinases , while GATA 3 notably blocks PU . 1 and IL 7Ralpha expression , and PU . 1 reduces expression of HES 1 and c Myb . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The recombination activation genes , RAG 1 and RAG 2 , encode the critical components of the recombinase complex responsible for the generation of functional antigen receptor genes . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Recombination is initiated by the lymphoid specific RAG 1 and RAG 2 proteins , which cooperate to make double strand breaks at specific recognition sequences ( recombination signal sequences , RSSs ) . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
A population of peripheral B cells have been shown to express recombination activating gene products , RAG 1 and RAG 2 , which are considered to be involved in revising the B cell antigen receptor ( BCR ) in the periphery . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RESULTS : Analysis of bulk mRNA indicated that RAG 1 and RAG 2 mRNA were found routinely in peripheral B cells of patients with active SLE , but not in healthy subjects . ^^^ When assessed on a single cell basis , there was a 3 fold increase in the frequency of RAG 1 and RAG 2 expressing B cells in SLE patients compared with healthy subjects . ^^^ Notably , B cells expressing both RAG 1 and RAG 2 mRNA expressed only IgD mRNA , but not IgG mRNA . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The RAG 1 and RAG 2 proteins are the lymphoid specific factors essential for 5 ( D ) J recombination , the process that leads to the diversification of antigen receptors on B and T lymphocytes . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Recombination of gene segments at the immunoglobulin and T cell receptor loci requires that the RAG 1 and RAG 2 proteins bring together DNA signal sequences ( RSSs ) with 12 and 23 bp spacers into a synaptic complex and cleave the DNA . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Sequence conservation of RAG 1 and RAG 2 genes in hematologic malignancies . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The protein products of the recombination activating genes ( RAG 1 and RAG 2 ) initiate the formation of immunoglobulin ( Ig ) and T cell receptors , which are essential for B and T cell development , respectively . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Signaling initiated via the preBCR promotes cellular proliferation and RAG 1 and RAG 2 downregulation to interrupt the immunoglobulin 5 ( D ) J gene rearrangement process . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
In 5 ( D ) J joining of antigen receptor genes , two recombination signal sequences ( RSSs ) , 12 RSS and 23 RSS , are paired and complexed with the protein products of recombination activating genes RAG 1 and RAG 2 . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Our results showed that low levels of RAG 1 and RAG 2 mRNA were present in all T cell subpopulations except CD 3 ( + ) / CD4 ( ) T cells . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
By stroma replacement from MSS 62 cells to TBR 31 1 cells , DFC 28 cells were differentiated into very early B lymphoid stage characterized by c kit down regulation and induction of BP 1 and B lymphoid associated genes ( Pax 5 , CD 19 , TdT , Rag 1 , and Rag 2 ) . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
A RAG 1 / RAG 2 tetramer supports 12 / 23 regulated synapsis , cleavage , and transposition of 5 ( D ) J recombination signals . ^^^ Initiation of 5 ( D ) J recombination involves the synapsis and cleavage of a 12 / 23 pair of recombination signal sequences by RAG 1 and RAG 2 . ^^^ In the absence of HMG 1 , 1 found that two discrete RAG 1 / RAG 2 complexes are detected by mobility shift assay on all RSS substrates tested . ^^^ Both contain dimeric RAG 1 and either one or two RAG 2 subunits . ^^^ The addition of HMG 1 supershifts both complexes without altering the RAG protein stoichiometry . 1 find that 12 / 23 regulated recombination signal synapsis and cleavage are only supported in a protein DNA complex containing HMG 1 and a RAG 1 / RAG 2 tetramer . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Patients with mutations of either RAG 1 or RAG 2 genes suffer from severe combined immunodeficiency ( SCID ) characterized by the lack of T and B lymphocytes . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Previous in vitro studies defined the minimal regions of RAG 1 and RAG 2 essential for 5 ( D ) J recombination . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Inverse transposition by the RAG 1 and RAG 2 proteins : role reversal of donor and target DNA . ^^^ The lymphoid specific proteins RAG 1 and RAG 2 initiate 5 ( D ) J recombination by introducing DNA double strand breaks at the recombination signal sequences ( RSSs ) . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Finally , purified core RAG 1 and RAG 2 proteins ( together with HMG 2 ) also reproduce B12 / 23 restriction in a cell free system . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
A mutant truncated RAG 2 protein ( `` core ' ' RAG 2 ) lacking the C terminal 144 amino acids , together with core RAG 1 , is able to mediate the basic biochemical steps required for 5 ( D ) J recombination in vitro and in transfected cell lines . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
In common with other vertebrate species , the shark RAG 2 coding region lacks introns and is closely linked in opposite orientation to the RAG 1 gene . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
These DNA rearrangements involve cleavage by the RAG 1 and RAG 2 ( RAG1 / 2 ) recombinase enzymes at recombination signal sequences ( RSS ) . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 initiate 5 ( D ) J recombination , which is the assembly of immunoglobulin and T cell receptor genes . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
In analogy to human MLL , MLL ENL transformed cells not only coexpressed lymphocyte specific ( rag 1 , rag 2 , pax 5 , Tdt ) and monocyte specific genes ( lysozyme , c fms ) , but also showed rearrangements of the genomic immunoglobulin locus . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 initiate 5 ( D ) J recombination by introducing DNA double strand breaks between each selected gene segment and its bordering recombination signal sequence ( RSS ) in a two step mechanism in which the DNA is first nicked , followed by hairpin formation . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Therefore , CD 40 regulated expression of RAG 1 and RAG 2 in peripheral T cells may constitute a novel pathway for the generation of autoaggressive T cells . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 catalyze the initial DNA cleavage steps in 5 ( D ) J recombination . ^^^ Furthermore , core RAG 2 ( residues 1 387 ) formed complexes with multimeric RAG 1 species bound to a single RSS , providing additional support for the physiological relevance of higher order oligomeric states of RAG1 . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The RAG 1 and RAG 2 proteins perform critical DNA recognition and cleavage functions in 5 ( D ) J recombination , and also catalyze efficient DNA transposition in vitro . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Truncated forms of RAG 1 and RAG 2 are functional in vivo and have been used to study 5 ( D ) J cleavage , hybrid joint formation and transposition in vitro . ^^^ Although full length RAG 1 and RAG 2 proteins rarely form hybrid joints in vivo in the absence of non homologous end joining factors , we show that the full length proteins alone can catalyze this reaction in vitro . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Two lymphoid specific proteins , RAG 1 and RAG 2 , are required for the initiation of the 5 ( D ) J recombination in vitro . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
In vitro binding and cleavage assays using recombinant RAG 1 and RAG 2 proteins further validated the cRSS participation in this RAG mediated recombination process . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Thus , bone marrow TLPs are heterogenous with respect to TCRbeta rearrangement status , suggesting an active recombination machinery that is consistent with the expression of RAG 1 , RAG 2 , and TdT in this population . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Transcript expression of two Iglambda rearrangements and RAG 1 / RAG 2 in a mature human B cell producing IgMlambda islet cell autoantibody . ^^^ RAG 1 and RAG 2 transcripts occurred in EBV MB 91 but not in HY MB 91 , indicating that the former but not the latter might have been able to exhibit 5 ( D ) J recombinase activity . ^^^ Data show that a mature nonmalignant human B cell clone producing IgMlambda ICA can express RAG 1 / RAG 2 transcripts . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Expression of the recombinase proteins RAG 1 and RAG 2 is discordant : while RAG 1 is relatively long lived , RAG 2 is degraded periodically at the G ( 1 ) S transition . ^^^ RAG 1 or RAG 2 , expressed individually , is a nuclear protein . ^^^ RAG 1 rescued the localization of degradation defective , RAG 2 NLS mutants ; this required an intact RAG 1 NLS . ^^^ Recombination defects were correlated with a cell cycle dependent defect in the ability of RAG 1 to rescue localization of the RAG 2 mutants . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Recombination activating gene products , RAG 1 and RAG 2 , bind and cleave the cRSS to generate DNA deletion circles during the 5 ( H ) replacement process . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Although expression of the RAG 1 and RAG 2 genes is essential for lymphocyte development , the mechanisms responsible for the lymphoid and developmental stage specific regulation of these genes are poorly understood . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RT PCR and Western blotting were used to examine the expression of SNC 73 , recombination activating gene 1 ( RAG 1 ) , and RAG 2 . ^^^ RESULTS : The human epithelial cancer cell line ( SW 480 ) positively expressed SNC 73 , RAG 1 , and RAG 2 . ^^^ Both sequencing and Western blotting showed that the RAG 1 and RAG 2 expressed in SW 480 cells were identical to that expressed in pre B lymphocytes . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Here , we show that expression in Saccharomyces cerevisiae of murine RAG 1 and RAG 2 , the lymphoid specific components of the 5 ( D ) J recombinase , is sufficient to induce 5 ( D ) J cleavage and rejoining in this lower eukaryote . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The 5 ( D ) J recombination of TCRalpha and beta in early developing T cells is a highly modulated phenomenon initiated and completed by recombinase complex ( RAG 1 and RAG 2 ) , and regulated by other gene products such as interleukins . ^^^ To further evaluate the association of several other gene products with the evolution of TCRVbeta8 . 1 5 ( D ) J rearrangements in vivo , the mRNA expression levels of seven interleukins , three cytokines , receptors TCRVbeta8 . 1 and IL 2Rbeta , MHC I / MHC 2 , RAG 1 / RAG 2 and retroviral superantigen MMTV ( SW ) were measured by RT PCR during the fetal development of the thymus of three inbred mouse strains ( Balb c , C57B1 / 6 and CBA / J ) . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 are the lymphocyte specific components of the 5 ( D ) J recombinase . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Full length RAG 2 , and not full length RAG 1 , specifically suppresses RAG mediated transposition but not hybrid joint formation or disintegration . ^^^ RAG 1 and RAG 2 initiate 5 ( D ) J recombination by introducing DNA breaks at recombination signal sequences flanking a pair of antigen receptor gene segments . ^^^ From mammalian cells , full length RAG 1 is readily purified with core RAG 2 but not full length RAG 2 and vice versa . ^^^ Despite differences in DNA binding activity , recombinase containing either core or full length RAG 1 or RAG 2 possess comparable cleavage , rejoining , and end processing activity , as well as similar usage preferences for canonical versus cryptic recombination signals . ^^^ However , recombinase containing full length RAG 2 , but not full length RAG 1 , exhibits dramatically reduced transposition activity in vitro . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Using DNA microarrays and Northern blots to analyze unstimulated cells , we demonstrate that expression of a cluster of genes , including RAG 1 and RAG 2 , is repressed by constitutive signals requiring the adapter molecules LAT and SLP 76 . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Normal B cells did not express RAG 1 and RAG 2 spontaneously . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Here we review the prevalence of autoantibodies in the initial antibody repertoire , their regulation by receptor editing , and the role of the recombinase proteins ( RAG 1 and RAG 2 ) in this process . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
We determined DNA sequences of the nuclear encoded recombination activating genes ( Rag 1 and Rag 2 ) from all three major lungfish groups , the Australian Neoceratodis forsteri , the South American Lepidosiren paradoxa and the African lungfish Protopterus dolloi , and the Indonesian coelacanth Latimeria menadoensis . ^^^ Phylogenetic analyses of both the single gene and the concatenated data sets of RAG 1 and RAG 2 found that the lungfishes are the closest living relatives of the land vertebrates . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
We have identified a silencer and an antisilencing element that interact at a distance of 85 kilobases to regulate expression of the recombination activating genes Rag 1 and Rag 2 in thymocytes . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
During 5 ( D ) J recombination , the RAG 1 and RAG 2 proteins form a complex and initiate the process of rearrangement by cleaving between the coding and signal segments and generating hairpins at the coding ends . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Here we report that RAG 1 and RAG 2 proteins in the signal end ( SE ) complex cleave the 3 ' overhanging structure of the synthetic coding end ( CE ) DNA in two successive steps in vitro . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Cell cycle dependent accumulation in vivo of transposition competent complexes between recombination signal ends and full length RAG proteins . 5 ( D ) J recombination is initiated by a specialized transposase consisting of RAG 1 and RAG 2 . ^^^ Because full length RAG proteins are insoluble under physiologic conditions , most previous analyses of RAG activity in vitro have used truncated core RAG 1 and RAG 2 fragments . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
We have tested the ability of this system to drive functional expression in vivo of the 5 ( D ) J recombination activating genes , RAG 1 and RAG 2 . ^^^ In induced transgenic mice , transgenic RAG 1 and RAG 2 mRNA is observed in thymus and spleen , and expression of both transgenes on the RAG 1 or RAG 2 knockout backgrounds allows partial , inducible , lymphocyte reconstitution . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Mutations in genes required for T cell development : IL7R , CD 45 , IL2RG , JAK 3 , RAG 1 , RAG 2 , ARTEMIS , and ADA and severe combined immunodeficiency : HuGE review . ^^^ Mutations in any of eight known genes : IL2RG , ARTEMIS , RAG 1 , RAG 2 , ADA , CD 45 , JAK 3 , and IL7R cause SCID . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
A spontaneous mutation in DNA PKcs of BALB / c mice results in SCID , as do experimentally induced mutations in RAG 1 and RAG 2 . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
It has been recently shown that mutations in both of the recombination activating genes RAG 1 and RAG 2 are involved in each of the two different types of severe combined immunodeficiency ( SCID ) syndromes : T B SCID and Omenn ' s syndrome ( OS ) . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The acquisition of the capability of heterophilic antigen binding mode of interaction was apparently related to the introduction of recombination activating retroviral genes ( RAG 1 and RAG 2 ) into the genome of Gnathostomata ancestors . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The HARBI 1 proteins are conserved in humans , rats , mice , cows , pigs , chickens , frogs , and various bony fish , as well as other extremely important proteins , including RAG 1 and RAG 2 . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
It has been suggested that pre B cell receptor ( pre BCR ) signals are responsible for down regulation of the VDJH recombinase machinery ( Rag 1 , Rag 2 , and terminal deoxynucleotidyl transferase [ TdT ] ) , thereby preventing further rearrangement on the second HC allele . ^^^ Using a mouse model , we show that expression of an inducible muHC transgene in Rag 2 / pro B cells induces down regulation of the following : ( a ) TdT protein , ( b ) a transgenic green fluorescent protein reporter reflecting endogenous Rag 2 expression , and ( c ) Rag 1 primary transcripts . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
As is observed on naked DNA , in the presence of core RAG 1 , the full length RAG 2 protein proved to be more active than core RAG 2 on these polynucleosomal arrays , reinforcing the importance of the RAG 2 C terminal domain for efficient recombination . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Joining mutants of RAG 1 and RAG 2 that demonstrate impaired interactions with the coding end DNA . ^^^ In 5 ( D ) J joining of antigen receptor genes , two recombination signal sequences ( RSSs ) , 12 and 23 RSSs , form a complex with the protein products of recombination activating genes , RAG 1 and RAG 2 . ^^^ Joining mutants of RAG 1 and RAG 2 demonstrate impaired interactions with the coding region in both pre and postcleavage type complexes . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 1 and / or RAG 2 RNA was detected in PBMCs from 42 % of patients with IM but not from healthy control subjects . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 play a central role in 5 ( D ) J recombination , a process for antigen receptor gene assembly . ^^^ To investigate the role of the non core regions of RAGs in the end joining phase of antigen receptor rearrangement , we analyzed recombination products isolated from core RAG 1 and core RAG 2 knock in mice . ^^^ Signal joints ( SJs ) associated with 5 to D recombination of core RAG 1 knock in mice were normal , whereas those of core RAG 2 knock in mice were highly imprecise , containing large deletions and additions , and in some cases coding sequences . ^^^ In contrast , we found an elevated level of imprecise D to J associated SJs for both core RAG 1 and RAG 2 expressing mice . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Synapsis of recombination signal sequences located in cis and DNA underwinding in 5 ( D ) J recombination . 5 ( D ) J recombination requires binding and synapsis of a complementary ( 12 / 23 ) pair of recombination signal sequences ( RSSs ) by the RAG 1 and RAG 2 proteins , aided by a high mobility group protein , HMG 1 or HMG 2 . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Phylogenies based on over 2000 bp of two nuclear genes ( Rag 1 and Rag 2 ) identified reliably a clade of the Mantella betsileo and Mantella laevigata groups as sister lineage to the M . madagascariensis group , but did not support species within the latter group as monophyletic . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Intestinal samples from infants less than 6 mo old contained transcripts of T early alpha and TdT , and 15 of 19 infant samples contained mRNA for RAG 1 , some coexpressing RAG 2 . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
To further investigate the phylogenetic intrarelationships of discoglossids , nucleotide sequences of four nuclear protein coding genes ( CXCR 4 , RAG 1 , RAG 2 , and Rhodopsin ) with sequences available for the three discoglossid genera and Xenopus were retrieved from GenBank , and together with a concatenated nucleotide sequence data set containing all mt protein coding genes except ND 6 were subjected to separate and combined phylogenetic analyses . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
STI 571 treatment of leukemia patients induced expression of the Ig L chain associated transcription factors IRF 4 and SPIB , up regulation of RAG 1 and RAG 2 , Ckappa and Clambda germline transcription , and rearrangement of Ig kappa L chain ( IGK ) and Ig lambda L chain ( IGL ) genes . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RESULTS : TdT , RAG 1 , and RAG 2 were variably expressed . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
We will also discuss the consequences of integration in the genome by rag 1 and rag 2 genes ( recombination activating genes ) . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
In humans , most T ( ) B ( ) severe combined immunodeficiencies ( SCID ) have a defect in either the RAG 1 or RAG 2 gene , are not radiosensitive and do not show genome instability . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
In this study , we present evidence that activated mature CD 5 positive human tonsil B cells coexpress both RAG 1 and RAG 2 mRNA and protein , and display DNA cleavage resulting from their recombinase activity . ^^^ Furthermore , in vitro activation of CD 5 negative naive mature B cells by IgR and CD 40 cross linking induces expression of CD 5 on a subset of cells , and leads to the up regulation of RAG 1 and RAG 2 only in cells turned positive for CD 5 . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
In particular , PBR expression induced several differentiation markers ( such as CD 1 , CD 6 ) , or key regulating elements ( e . g . , RAG 1 , RAG 2 , CD 99 , TCR ) . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
This site specific recombination reaction is initiated by a complex containing the RAG 1 and RAG 2 proteins and completed by general DNA repair factors . ^^^ RAG 1 and RAG 2 , like the adaptive immune system itself , are found exclusively in jawed vertebrates , and are thought to have entered the vertebrate genome by horizontal transmission as components of a transposable element . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
OS patients carry leaky mutations of recombination activating genes ( RAG 1 or RAG 2 ) resulting in partial 5 ( D ) J recombination activity , whereas null mutations cause severe combined immunodeficiency with absence of mature T and B cells ( T B SCID ) . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The 5 ( D ) J recombination reaction in jawed vertebrates is catalyzed by the RAG 1 and RAG 2 proteins , which are believed to have emerged approximately 500 million years ago from transposon encoded proteins . ^^^ Yet no transposase sequence similar to RAG 1 or RAG 2 has been found . ^^^ We also suggest that the RAG 2 protein was not encoded by ancient Transib transposons but emerged in jawed vertebrates as a counterpart of RAG 1 necessary for the 5 ( D ) J recombination reaction . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
In addition , re expression of RAG 1 and RAG 2 in TCRbeta ( + ) cells is impaired , and the Valpha repertoire is altered . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The RAG 1 and RAG 2 proteins catalyze 5 ( D ) J recombination and are essential for generation of the diverse repertoire of antigen receptor genes and effective immune responses . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Carp rag 1 and rag 2 showed 90 and 89 % amino acid identity , respectively , to the corresponding zebrafish sequences . ^^^ From 1 wpf , rag 1 / rag 2 was expressed in kidney ( together with immunoglobulin heavy chain expression ) but not in spleen , while WCI12+ cells appeared 1 week later in both organs , suggesting B cell recombination in kidney but not in spleen . ^^^ Rag 1 expression exceeded rag 2 levels in thymus and in head and trunk kidney of juveniles , but this ratio was reversed in head and trunk kidney from approximately 16 wpf onwards . ^^^ Rag 1 / rag 2 expression was detected in thymi of animals over 1 year old , but in kidney only at low levels , indicating life long new formation of putative T cells but severely reduced formation of B cells in older fish . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The original rag allele found in W 50 was renamed rag 1 , while three novel alleles , rag 2 to rag 4 , were found in isolates lacking rag 1 . ^^^ In a laboratory collection of 168 isolates , 26 % carried rag 1 , 36 % carried rag 2 , 25 % carried rag 3 , and 14 % carried rag 4 ( including the type strain , ATCC 33277 ) . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Analysis of nuclear ( rag 1 , rag 2 , and rhodopsin genes ) and mitochondrial markers ( 12S and 16S ribosomal RNA genes ) provide evidence for an endemic clade of African genera of high morphological and ecological diversity thus far assigned to up to five different subfamilies : Afrana , Cacosternum , Natalobatrachus , Pyxicephalus , Strongylopus , and Tomopterna . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 initiate 5 ( D ) J recombination through synapsis and cleavage of a 12 / 23 pair of 5 ( D ) J recombination signal sequences ( RSS ) . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
In vertebrates , a diverse repertoire of antigen specific receptors , T cell receptors and immunoglobulins is generated by 5 ( D ) J recombination performed by the RAG 1 and RAG 2 protein complex . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
OBJECTIVE : The recombination activating enzymes RAG 1 and RAG 2 are essential to the process of 5 ( D ) J rearrangement in B and T cells and thus to the development of normal immune function . ^^^ Mutations in RAG 1 or RAG 2 can lead to a spectrum of disorders , ranging from typical ( B ) ( T ) severe combined immunodeficiency to Omenn ' s syndrome . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The DNA lesions can be introduced either by specific factors ( RAG 1 and RAG 2 in the case of 5 ( D ) J recombination and AID in the case of CSR and SHM ) or during the various phases of cellular proliferation and cellular activation . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Severe combined immunodeficiency ( SCID ) caused by mutations in RAG 1 or RAG 2 genes is characterized by a complete block in T and B cell development . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Transcripts of the RAG 1 and RAG 2 genes and earlier defined transcription factors , such as E2A , early B cell factor , E 2 2 , PAX 5 , and IRF 4 , were specifically up regulated at stages undergoing Ig gene rearrangements . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Amorphic mutations in the recombination activating genes RAG 1 and RAG 2 have been reported to cause T B SCID , whereas hypomorphic mutations led to the expansion of a few autoimmune T cell clones responsible for the Omenn syndrome phenotype . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Here we expand the molecular data to include DNA sequences , totaling 6192 base pairs ( bp ) , from nine nuclear protein coding genes ( C mos , RAG 1 , RAG 2 , R 35 , HOXA 13 , JUN , alpha enolase , amelogenin and MAFB ) for 19 taxa representing all major lineages . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 cleave DNA to generate blunt signal ends and hairpin coding ends at antigen receptor loci in lymphoid cells . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Moreover , deletion of either the RAG 2 or RAG 1 genes in B 6 mice was not associated with increased neuronal death at day 14 post axotomy , as we had previously found in B 6 mice with the severe combined immunodeficiency ( SCID ) mutation . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Transposition events into the target episome , accompanied by characteristic target site duplications , were detected at a low frequency using RAG 1 and either truncated `` core ' ' RAG 2 or full length RAG 2 . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The reaction , and its crucial mediators RAG 1 and RAG 2 , are essential for lymphocyte development and hence for adaptive immunity . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The Rag 1 and Rag 2 proteins are the key mediators of this process . ^^^ Here , we identify and characterize a closely linked pair of genes , SpRag1L and SpRag2L , from an invertebrate , the purple sea urchin ( Strongylocentrotus purpuratus ) with similarity in both sequence and genomic organization to the vertebrate Rag 1 and Rag 2 genes . ^^^ They are coexpressed during development and in adult tissues , and recombinant versions of the proteins form a stable complex with each other as well as with Rag 1 and Rag 2 proteins from several vertebrate species . ^^^ We thus conclude that SpRag1L and SpRag2L represent homologs of vertebrate Rag 1 and Rag 2 . ^^^ In combination with the apparent absence of 5 ( D ) J recombination in echinoderms , this finding strongly suggests that linked Rag 1 and Rag 2 like genes were already present and functioning in a different capacity in the common ancestor of living deuterostomes , and that their specific role in the adaptive immune system was acquired much later in an early jawed vertebrate . . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
DNA cleavage of a cryptic recombination signal sequence by RAG 1 and RAG 2 . ^^^ Recombination is initiated by cleavage of conserved recombination signal sequences ( RSS ) by RAG 1 and RAG 2 during lymphocyte development . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
Moreover , Pax 5 interacted with the recombination activating gene 1 ( RAG 1 ) RAG 2 complex to enhance RAG mediated 5 ( H ) recombination signal sequence cleavage and recombination of a 5 ( H ) gene substrate . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 initiate 5 ( D ) J recombination by cleaving DNA at recombination signal sequences through sequential nicking and transesterification reactions to yield blunt signal ends and coding ends terminating in a DNA hairpin structure . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
The generation of developing B cells in the bone marrow is regulated by recombination activating genes RAG 1 and RAG 2 proteins . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
We correlate this arrest with up regulation of Bcl 2 , CD 2 , CD 5 , and CD 27 proteins and constitutive activation of NFAT but a severe impairment of Rag 1 , Rag 2 , and intracellular TCR beta as well as intracellular TCR gammadelta protein expression . ^^^ A correlation between the loss of NFAT activity and Rag 1 and Rag 2 expression is also found in myristoylated PKB induced CD4+ lymphoma cells . ^^^ Furthermore , ectopic expression of NFAT inhibits Rag 2 promoter activity in EL 4 cells , and in vivo binding of NFATc 1 to the Rag 1 and Rag 2 promoter and cis acting transcription regulatory elements is verified by chromatin immunoprecipitation analysis . ^^^ |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P15918 and P55895 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :1.0002167 |
This finding reinforces the biological significance of this predicted model and suggests that RAG 1 interacts with RAG 2 on one of the side of the scaffold formed by the beta propeller . . 1.0002167^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.54407654 |
However , both mutations reduce the capacity of RAG 2 to interact with RAG 1 and block recombination signal cleavage , therefore implicating a defect in the early steps of the recombination reaction as the basis of the clinical phenotype . 0.54407654^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.65210829 |
RSS induced conformational changes of StrRAG 1 may influence the interaction of RAG 1 with RAG 2 and synaptic complex formation . . 0.65210829^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.55501808 |
Amino acid residues in RAG 1 responsible for the interaction with RAG 2 during the 5 ( D ) J recombination process . 0.55501808^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Human RAG 2 , like RAG 1 , is on chromosome 11 band p 13 and therefore not linked to ataxia telangiectasia complementation groups . ^^^ Here we report the location of a human recombination activating gene ( RAG 2 ) , in addition to RAG 1 , on chromosome 11 , band p 13 , thereby formally demonstrating linkage of these genes in humans and showing that they are not linked to the known locus responsible for the A T syndrome . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Furthermore , the recombination activating genes RAG 1 and RAG 2 are differentially expressed , with RAG 2 detectable only by polymerase chain reaction , implying that very low levels of one of these gene products are sufficient to complement the other to facilitate VJ rearrangements . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Thus , the surface expression of an alpha beta TCR does not prevent further alpha TCR rearrangement in immature thymocytes that still transcribe RAG 1 and RAG 2 genes . ^^^ Reduced levels of RAG 1 and RAG 2 RNA are detectable only in CD4+8+ TCR high cells , which result from positive selection in the thymus . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
EBV DNA positive and negative HD cases with numerous SR cells lack significant mRNA expression of the two recombinase activating genes ( RAG 1 and RAG 2 ) . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Stable hybrids between the scid pre B and the myeloma cells had lost the expression of RAG 1 and RAG 2 genes , supporting the previous finding of an inhibitor of rearrangement in myeloma cells that acts shortly after fusion . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Northern ( RNA ) blot analysis of the expression of the MB 1 , lambda 5 , Vpre B , c mu , RAG 1 , and RAG 2 genes in pro B and pre B clones show that transcription of the MB 1 gene precedes IgH gene rearrangement and RNA synthesis from c mu , RAG 1 , RAG 2 , lambda 5 , and Vpre B genes . ^^^ All clones at the pre B cell stage synthesize mRNA for c mu , RAG 1 , and RAG 2 genes ; transcription of the lambda 5 and Vpre B genes seems to start after D to JH rearrangement in B cell precursors , indicating that the proteins encoded by either gene are not required for B cell progenitors to undergo D to JH gene rearrangement . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The recombination activating genes RAG 1 and RAG 2 are required for 5 ( D ) J DNA rearrangements at loci for immunoglobulin and T cell receptor genes . ^^^ Mapping analysis of RAG 1 and RAG 2 genes on human chromosomes by fluorescence in situ hybridization indicated that the genes are located on chromosome 11p13 p 12 . ^^^ RAG 1 and RAG 2 do not seem to be linked to any of the primary immunodeficiencies for which defective genes have already been mapped . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Expression of human recombination activating genes ( RAG 1 and RAG 2 ) in Hodgkin ' s disease . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The 5 ( D ) J recombinase activating genes , RAG 1 and RAG 2 , are coexpressed only in immature lymphocytes , and are sufficient and necessary for 5 ( D ) J recombination to occur in non lymphoid cells . ^^^ In order to examine control mechanisms operative in the regulation of RAG 1 and RAG 2 , we have studied the pattern of expression of these genes in human pre T cells , pre B cells , and thymocytes treated with the phorbol ester 12 O tetradecanoylphorbol 13 acetate ( TPA ) ; an agent which mimics some of the lymphocyte maturation changes seen in vivo . ^^^ The expression of RAG 1 and RAG 2 was tightly controlled in a rapid , yet very complex , manner with both positive and negative control elements operating . ^^^ Treatment of immature lymphocytes with TPA caused the specific and rapid elimination of steady state RAG 1 and RAG 2 RNA . ^^^ A labile transcriptional repressor , separate from the TPA associated repression of transcription , was also active in cells transcribing RAG 1 and RAG 2 RNA . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Activation of 5 ( D ) J recombination by RAG 1 and RAG 2 . 5 ( D ) J recombination is normally limited to lymphoid cells , but expression of the RAG 1 and RAG 2 genes allows other cell types to carry out this reaction . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Using a transient transfection assay , we demonstrate that the recombination activating genes Rag 1 and Rag 2 direct site specific rearrangement on an artificial substrate in poorly differentiated as well as in differentiated nonlymphoid cell lines . ^^^ N region insertions , which are characteristic of adult junctional diversity , are obtained at high frequency upon transfection of a terminal deoxynucleotidyltransferase expression vector together with Rag 1 and Rag 2 . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The RAG 1 and RAG 2 genes synergistically confer VDJ recombinase activity to nonlymphoid cell lines . ^^^ Levels of RAG 1 and RAG 2 expression in primary murine lymphoid tissues and lymphoid bone marrow cultures generally are much higher than those of transformed precursor B cell lines . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
In TCR / CD3 thymocytes , CD 2 stimulation also failed to affect steady state mRNA levels of the recombination activating genes RAG 1 and RAG 2 , whereas in TCR / CD3+ cells activation of the CD 2 pathway terminated their expression . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
In an attempt to determine the distribution of recombinase activity in the mouse thymus , spleen and lymph nodes , we used the in situ hybridization method to examine the expression of the recombination activating genes RAG 1 and RAG 2 . ^^^ Although hybridization signals of RAG 2 were not as intense as those of RAG 1 , the localization of RAG 2 transcripts was similar to that of RAG 1 . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
We report here that B cell lines derived from these tumors , as well as a line derived from 5 myc retroviral transformation , simultaneously express surface immunoglobulin ( a hallmark of mature B cells ) as well as a common subset of genes normally restricted to the pre B stage of development including the recombinase activating genes RAG 1 and RAG 2 . ^^^ Continued RAG 1 and RAG 2 expression in these lines is associated with VDJ recombinase activity detected with a VDJ recombination substrate . ^^^ Cross linking of the surface immunoglobulin on these lines with an anti mu antibody leads to rapid , specific and reversible down regulation of RAG 1 and RAG 2 gene expression . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Evidence was obtained for genetic linkage between the T 160 gene and the recombination activator genes RAG 1 and RAG 2 . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Two tightly linked recombination activating genes , RAG 1 and RAG 2 , are involved in VDJ recombination of the immune system . ^^^ It remains to be seen whether expression of RAG 1 and RAG 2 in CNS is abortive or functionally important . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The effect of cAMP agonists on recombination appears to reflect an increase in cellular recombination activity , as indicated by the caffeine induced rise in the level of mRNA from the recombination activating genes RAG 1 and RAG 2 . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Germ line kappa light chain gene transcription and rearrangement were unaffected , but transcription of the recombination activating genes RAG 1 and RAG 2 and the lymphoid specific transcription factor Oct 2 was increased . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The recombination activating genes , RAG 1 and RAG 2 , are on chromosome 11p in humans and chromosome 2p in mice . ^^^ The recombination activating genes RAG 1 and RAG 2 are adjacent genes that act synergistically to activate variable diversity joining ( 5 ( D ) J ) recombination . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Stable pre B cell 10 myeloma hybrids that retained the critical myeloma chromosomes were found to have lost VDJ recombinase activity and transcripts of the RAG 1 , RAG 2 and TdT genes . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Among three mRNAs encoding putative recombinase proteins , RAG 1 and RAG 2 mRNAs were not expressed in any cell lines tested , while RBP 2 mRNA was expressed ubiquitously . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The recombination activating genes , RAG 1 and RAG 2 , are likely to encode components of the 5 ( D ) J site specific recombination machinery . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Therefore , we have examined the potential role of the 5 ( D ) J recombination activating genes , RAG 1 and RAG 2 , in regulating chicken Ig gene conversion . ^^^ In contrast to the coexpression of RAG 1 and RAG 2 observed in mammalian B cells that undergo 5 ( D ) J recombination , chicken B cells isolated from the bursa of Fabricius express high levels of the RAG 2 mRNA but do not express RAG 1 mRNA . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Thymocyte expression of RAG 1 and RAG 2 : termination by T cell receptor cross linking . ^^^ The expression of the 5 ( D ) J [ variable ( diversity ) joining elements ] recombination activating genes , RAG 1 and RAG 2 , has been examined during T cell development in the thymus . ^^^ In situ hybridization to intact thymus and RNA blot analysis of isolated thymic subpopulations separated on the basis of T cell receptor ( TCR ) expression demonstrated that both TCR and TCR+ cortical thymocytes express RAG 1 and RAG 2 messenger RNA ' s . ^^^ Thus , although cortical thymocytes that bear TCR on their surface continue to express RAG 1 and RAG 2 , it appears that the expression of both genes is normally terminated during subsequent thymic maturation . ^^^ Consistent with this hypothesis , thymocyte TCR cross linking in vitro led to rapid termination of RAG 1 and RAG 2 expression , whereas cross linking of other T cell surface antigens such as CD 4 , CD 8 , or HLA class 1 had no effect . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Expression of human recombination activating genes ( RAG 1 and RAG 2 ) in neoplastic lymphoid cells : correlation with cell differentiation and antigen receptor expression . ^^^ Recently , two genes , RAG 1 and RAG 2 , that are able to activate rearrangement of synthetic recombination substrates were cloned in mouse and a human gene homologous to RAG 1 was described . ^^^ To define the differentiation stages corresponding to RAG 1 and RAG 2 RNA expression , we have studied a large number of B and T lymphoid neoplasias . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Two recently cloned genes , RAG 1 and RAG 2 , are sufficient to induce rearrangements of synthetic substrates when transfected into fibroblasts . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
A regulatory role for recombinase activating genes , RAG 1 and RAG 2 , in T cell development . ^^^ RAG 1 and RAG 2 are developmentally regulated genes that are essential for the assembly of antigen receptors in lymphoid cells . ^^^ Here we describe transgenic mice that carry RAG 1 and RAG 2 under the control of the proximal lck promoter . ^^^ Persistent expression of RAG 1 and RAG 2 was associated with incomplete thymopoiesis and profoundly compromised cellular immunity . ^^^ These effects required both RAG 1 and RAG 2 , since mice that carried either gene exclusively were indistinguishable from wild type controls . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
A simple technique for generating probes for RNA in situ hybridization : an adjunct to genome mapping exemplified by the RAG 1 / RAG 2 gene cluster . ^^^ As an example , we show that mRNA for the recombination activating genes ( RAG ) RAG 1 and RAG 2 is found in thymus of dE 16 mouse embryos . ^^^ Within the thymus , high levels of expression of RAG 1 and RAG 2 are detectable in the cortex but not in the medullary region . ^^^ This supports the view that RAG 1 and RAG 2 expression is associated with cells known to actively rearrange antigen receptor loci . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 , adjacent genes that synergistically activate 5 ( D ) J recombination . ^^^ RAG 1 inefficiently induced 5 ( D ) J recombinase activity when transfected into fibroblasts , but cotransfection with an adjacent gene , RAG 2 , has resulted in at least a 1000 fold increase in the frequency of recombination . ^^^ The 2 . 1 kilobase RAG 2 complementary DNA encodes a putative protein of 527 amino acids whose sequence is unrelated to that of RAG 1 . ^^^ Like RAG 1 , RAG 2 is conserved between species that carry out 5 ( D ) J recombination , and its expression pattern correlates precisely with that of 5 ( D ) J recombinase activity . ^^^ RAG 1 and RAG 2 might activate the expression of the 5 ( D ) J recombinase but , more likely , they directly participate in the recombination reaction . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 : nuclear genes involved in the dependence / independence on mitochondrial respiratory function for growth on sugars . ^^^ This phenotype was found to be controlled by two unlinked nuclear genes : RAG 1 and RAG 2 . ^^^ Either of their recessive alleles , rag 1 and rag 2 , led to the Rag phenotype ( i . e . the failure of growth on glucose in the presence of antimitochondrial drugs ) . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Epstein Barr virus induction of recombinase activating genes RAG 1 and RAG 2 . ^^^ In experimental B cell infections , Epstein Barr virus induced sustained expression of 5 ( D ) J recombinase activating genes RAG 1 and RAG 2 , whose aberrant activity has been implicated in chromosomal translocations in B cell neoplasms . ^^^ In cell lines in which RAG 1 and RAG 2 were detected , virus integrated into cellular DNA rather than assumed the configuration of extrachromosomal episomes . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Of 16 agents tested , only interleukin 7 ( IL 7 ) induced 5 ( D ) J gene rearrangement and sustained expression of the RAG 1 and RAG 2 genes , which are known to control rearrangement . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Although several groups have shown that such a signal may be required to down regulate RAG 1 and RAG 2 after a functional Ag receptor has been generated in early mature T or B cells , recently it has been suggested that under some circumstances , cross linking the B cell Ag receptor may result in up regulation of RAG expression . ^^^ To study this possibility , we used a unique set of cell variants isolated from a human mature B cell line , which differ in their expression of both the surface Ig receptor ( sIg ) and RAG 1 and RAG 2 genes . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Despite the essential and synergistic functions of the rag 1 and rag 2 proteins in 5 ( D ) J recombination and lymphocyte development , little is known about the biochemical properties of the two proteins . ^^^ Furthermore , the presence of rag 1 alters the behavior of rag 2 , conferring on it properties similar to those of rag 1 and changing its distribution in the nucleus . ^^^ We demonstrate that rag 1 and rag 2 are present in the same complex by coimmunoprecipitation , and we provide evidence that these complexes contain more molecules of rag 2 than of rag 1 . ^^^ The demonstration of intracellular complexes containing rag 1 and rag 2 raises the possibility that interaction between these proteins is necessary for their biological function . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Down regulation of RAG 1 and RAG 2 gene expression in preB cells after functional immunoglobulin heavy chain rearrangement . ^^^ The gene products of two recombination activating genes , RAG 1 and RAG 2 are crucial for this rearrangement process . ^^^ Here , we show that the expression of the RAG genes is twice up and down regulated , at the transcriptional level for RAG 1 and RAG 2 , and at the postranscriptional level for RAG 2 protein . ^^^ In immature B cells expressing on the cell surface RAG 1 and RAG 2 mRNA is down regulated , whereas RAG 2 protein levels are maintained . ^^^ Down regulation of RAG 1 and RAG 2 gene expression after productive rearrangement at one heavy chain allele might be part of the mechanisms that prevent further rearrangements at the other allele . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Our results show that a full length TCR delta transcript and the recombination activating genes RAG 1 and RAG 2 mRNA were already expressed in the CD34+1 subset . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
When used to drive expression of the recombination activating genes 1 and 2 ( RAG 1 and RAG 2 ) , the autoregulatory system yielded both substantially higher levels of variable ( diversity ) joining [ 5 ( D ) J ] recombination activity ( 70 fold on average ) and inducible expression in a much larger fraction of transfected cells ( autoregulatory , 90 % , vs . constitutive , 18 % ) . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
One genomic clone , lambda 4 , contained two RA genes , RAG 1 and RAG 2 . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Reflecting extrathymic T cell differentiation , MNC in the liver and pregnant uterus expressed mRNA of RAG 1 and RAG 2 . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 expression in human intestinal epithelium : evidence of extrathymic T cell differentiation . ^^^ When T lymphocytes undergo gene rearrangement , the products of both RAG 1 and RAG 2 genes are expressed ; RAG mRNA is present only in tissue governing lymphocyte maturation . ^^^ In this study , reverse transcription polymerase chain reaction ( RT PCR ) was used to detect RAG 1 and RAG 2 specific mRNA . ^^^ Primers for first round and nested PCR of RAG 1 and RAG 2 were synthesized . ^^^ RAG 1 and RAG 2 mRNA was detected in all bone marrow preparations but was absent in all peripheral blood samples . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
These results suggest that RAG 1 and RAG 2 are components of the 5 ( D ) J recombinase . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Expression of recombination activating genes ( RAG 1 and RAG 2 ) in Epstein Barr virus bearing B cells . ^^^ Recombination activating genes 1 and 2 ( RAG 1 and RAG 2 ) , are the only lymphoid specific genes required for the site directed recombination reaction leading to generation of B cell receptors and T cell receptors ( TCRs ) . ^^^ In EBV+ Burkitt ' s lymphoma lines , transcription of virus latent membrane protein 1 ( LMP 1 ) was correlated with downregulation of RAG 1 and RAG 2 . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
This rescue of scid B cell differentiation is associated with a dramatic reduction in expression of the recombination activation genes , RAG 1 and RAG 2 , and with reduced transcription of the kappa locus . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
In the postnatal period , both RAG 1 and RAG 2 genes are expressed at high levels in the RPL population . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
In a model system , RAG 1 and RAG 2 , the genes responsible for activating 5 ( D ) J recombination , were identified in a genomic transfectant by cDNA RDA in a small fraction of the time taken by conventional means . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Coordinate expression of two structurally distinct recombinase activating genes , RAG 1 and RAG 2 , is necessary for activation of site specific 5 ( D ) J recombination . ^^^ In mice bearing targeted disruptions of either the RAG 1 or RAG 2 genes , T and B lymphocyte development is arrested at the CD 4 8 double negative ( DN ) thymocyte or B220+ / CD43+ pro B cell stage . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Expression of human recombination activating genes ( RAG 1 and RAG 2 ) in lymphoma . ^^^ Two recently discovered genes , the recombination activating genes 1 and 2 ( RAG 1 and RAG 2 ) , are necessary to perform variable ( 5 ) , diversity ( D ) , and joining ( J ) recombination . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 gene expression and 5 ( D ) J recombinase activity are enhanced by protein phosphatase 1 and 2A inhibition in lymphocyte cell lines . ^^^ Expression of the recombination activating genes , RAG 1 and RAG 2 , in lymphocytes , has been shown to depend on second messenger systems . ^^^ The cell permeable tumor promoter , calyculin A ( CLA ) , which is a potent inhibitor of the type 1 and 2A serine / threonine protein phosphatases ( PP 1 and PP2A , respectively ) , was shown to upregulate the expression of RAG 1 and RAG 2 in pre B as well as mature B and T lymphocyte cell lines . ^^^ Moreover , in these mature lymphocyte cell lines there was no evidence of synergy in the regulation of RAG 1 and RAG 2 mRNA upon stimulation with CLA and caffeine . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
These events are accompanied by marked increases in the expression of RAG 1 and RAG 2 RNAs . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The recombinase activating genes , RAG 1 and RAG 2 , have been shown to be necessary to initiate the process of 5 ( D ) J recombination during the ontogeny of lymphocytes . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Recombinase activating genes ( RAG 1 and RAG 2 ) are expressed in immature T or B lymphocytes and possess activity to induce 5 ( D ) J rearrangement in TCR and Ig genes . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 are developmentally regulated genes that are essential for 5 ( D ) J recombination and lymphocyte development . ^^^ Expression of RAG 1 and RAG 2 by thymocytes is normally limited to cells that have not completed selection . ^^^ We find that neither selection nor TCR allelic exclusion can be overcome by transgenic expression RAG 1 and RAG 2 under the control of an lck promoter . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 are lymphoid specific genes that together induce 5 ( D ) J recombinase activity in a variety of nonlymphoid cell types . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
This process is highly regulated and mediated by the recombination activating proteins RAG 1 and RAG 2 . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
This event is accompanied by several changes classically associated with light chain gene rearrangement including increased activity of the NF kappa B transcription factor , expression of light chain RNAs and increased levels of expression of the RAG 1 and RAG 2 genes . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Although RAG 1 and RAG 2 have been shown to be indispensible for 5 ( D ) J recombination , their exact role in this reaction remains unclear . ^^^ Co transfecting RAG 1 and RAG 2 expression vectors into NIH3T3 fibroblasts confers 5 ( D ) J recombination activity to these otherwise recombinationally inactive cells . ^^^ In this report we have found that in transient transfections of mouse NIH3T3 fibroblasts with RAG 1 and RAG 2 and the appropriate recombination substrates , one RAG 1 expression vector , pRAG 1A , is capable of yielding both signal joints and coding joints , while another RAG 1 expression vector , pRAG 1B , yields only signal joints . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
These lymphoid cells expressed transcripts of the recombination activating genes , RAG 1 and RAG 2 , as well as the C mu gene , although the lymphoid cells did not express surface antigens specific to T or B lymphocytes such as T 200 , CD 4 , CD 8 and B 220 , or transcripts of B lymphocyte specific genes such as lambda 5 and mb 1 . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
We have assayed the 5 3 Chinese hamster ovary cell line , which has a double strand DNA break repair ( dsbr ) defect , for the ability to carry out 5 ( D ) J recombination following transfection of constructs that encode the RAG 1 and RAG 2 proteins necessary to confer 5 ( D ) J recombination activity to non lymphoid cells . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The products of the RAG 1 and RAG 2 genes are essential for the recombination of the DNA encoding the antigen receptors of the developing immune system . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
TCR rearrangement strictly depends upon the coordinate activity of two recombinase activating genes , Rag 1 and Rag 2 . ^^^ The results indicate that there are two periods of high Rag 1 and Rag 2 mRNA expression . ^^^ Active downregulation of Rag 1 and Rag 2 mRNA expression appears to occur in vivo between the two peaks of recombinase activity . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The recombination activating proteins RAG 1 and RAG 2 are both essential for this process , termed 5 ( D ) J rearrangement . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Unexpectedly , we found that overexpression of the FL zeta chain caused premature termination of RAG 1 and RAG 2 expression , prevented productive rearrangement of the TCR alpha and TCR beta genes and blocked entry of thymocytes into the CD4 / CD8 developmental pathway . ^^^ These results suggest that an early signaling pathway exists in precursor TCR thymocytes that can regulate RAG 1 and RAG 2 expression and is differentially responsive to individual members of the zeta family dimers . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Most significantly , the genes RAG 1 and RAG 2 , which are necessary for T cell receptor gene recombination to occur , are not expressed in liver T cells . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
While the parental cell line expressed low levels of the recombination activating genes , RAG 1 and RAG 2 , expression of these genes were considerably upregulated in both the immunoglobulin negative and the idiotypic variants . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Either RAG 1 or RAG 2 gene was not expressed in the B SCID derived cell lines . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The products of the RAG 1 and RAG 2 genes cooperate to allow 5 ( D ) J recombination in lymphoid and non lymphoid cells . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The recombinase activating genes RAG 1 and RAG 2 operate together to activate 5 ( D ) J recombination , and thus play an essential role in the generation of immune system diversity . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
We also show that IL 7 induced RAG 1 and RAG 2 mRNA expression by FL cells . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
In spite of the fact that CD 4 plays a critical role in thymocyte development , the abnormal signaling does not appear to influence thymocyte development at the stage when the T cell receptor is rearranged and the recombinase enzymes RAG 1 and RAG 2 transcripts are downregulated . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
In addition , detection of these broken ended signal sequences is dependent on the activity of RAG 1 and RAG 2 , and is restricted to the G0 / G1 phase of the cell cycle . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
No relationship of DSB rejoining to 5 ( D ) J recombinase activity was observed , since no mRNA hybridizing to the cDNA probes for RAG 1 or RAG 2 was detected in any of the cell lines tested . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 are not sufficient to direct all phases of immunoglobulin gene rearrangement in pre B cell lines . ^^^ Introduction of the RAG 1 and RAG 2 genes , genes encoding two such factors , failed to confer a rechi phenotype to these cells . ^^^ Neither the rechi phenotype nor kappa chain rearrangement correlated with levels of RAG 1 and RAG 2 expression in all of the hybrids . ^^^ Thus , both gene transfer and cell fusion experiments indicate that RAG 1 and RAG 2 are not sufficient to activate immunoglobulin gene recombination in at least some pre B cell lines . ^^^ In addition , the fusion experiments suggest that two gene products in addition to RAG 1 and RAG 2 may be required for kappa gene rearrangement . . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Northern analysis demonstrated that while the expression of the recombination activating genes RAG 1 and RAG 2 was relatively low in the parental cell line , their expression was significantly increased in both the sIg variants and their sIg+ progenies . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
R PCR also demonstrates expression of lambda 5 , RAG 1 and RAG 2 , which are specifically associated with pre B stage lymphocytes . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Dispensable sequence motifs in the RAG 1 and RAG 2 genes for plasmid 5 ( D ) J recombination . ^^^ As a probe of whether RAG 1 and RAG 2 gene products activate other genes or form part of the recombinase itself , certain mutants of the RAG genes were assayed for their ability to activate variable diversity joining region [ 5 ( D ) J ] recombination in a plasmid substrate in fibroblasts . ^^^ The results indicate that the N terminal one third of RAG 1 , including a zinc finger like domain , and an acidic domain of RAG 2 are dispensable for activating 5 ( D ) J recombination in a fibroblast , although they contribute quantitatively . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Transfection of fibroblasts from transgenic and control mice with the recombination activating genes , Rag 1 and Rag 2 , led to a high level of rearrangement of the hypomethylated transgenic , but not the endogenous chi genes . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Rag 1 and Rag 2 expression is also tightly regulated , and is found largely in the Pro B through small Pre B stages . ^^^ In contrast , lambda 5 , VpreB , Rag 1 , and Rag 2 are expressed at comparable levels . . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The recombination activating genes RAG 1 and RAG 2 appear to be necessary components of the machinery needed for the Ig or TCR gene rearrangements that occur in developing B and T lymphocytes . ^^^ Because gene conversion may be an important mechanism for 5 gene diversification in the rabbit , we cloned the rabbit RAG locus and characterized the coding regions of the genomic RAG 1 and RAG 2 . ^^^ In addition , we sequenced cDNAs encompassing the RAG 2 coding region , part of the RAG 2 5 ' untranslated region and a 967 bp fragment of cDNA from the RAG 1 coding region . ^^^ Northern analysis revealed a RAG 1 mRNA of 6 . 6 kb which is similar in size to the RAG 1 mRNA reported previously for other species , and a major species of RAG 2 mRNA of 4 . 4 kb , which is larger than that from the mouse ( 2 . 2 kb ) . ^^^ Analysis of the genomic clones showed that , as in other species , the RAG 1 and RAG 2 genes are oriented so as to be convergently transcribed . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Moreover , the expression of recombination activating genes 1 and 2 ( RAG 1 and RAG 2 ) also correlated with TCR gamma delta maturation as only HSA+ TCR gamma delta cells transcribed these genes . ^^^ Interaction of the HSA+ Tg+ TCR gamma delta cells with anti TCR gamma delta mAb or Ag bearing thymic stromal cells resulted in RAG 1 and RAG 2 down regulation . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Characterization and expression of recombination activating genes ( RAG 1 and RAG 2 ) in Xenopus laevis . ^^^ Two closely linked genes , RAG 1 and RAG 2 , are essential for this process , and have been identified in mice , humans , and chickens . ^^^ To study lymphocyte development in Xenopus laevis , we have characterized RAG 1 and RAG 2 in this species and examined their patterns of expression . ^^^ A product of expected size was obtained and used to identify a genomic clone that contained the complete coding region of RAG 1 ( 1045 codons ) , and approximately the 3 ' half of the coding region of RAG 2 . ^^^ The coding regions of RAG 1 and RAG 2 each lie on a single exon , are in opposite transcriptional orientation , and are separated by approximately 6 kb . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Here we show that early during the differentiation of pre B cells , upregulation of RAG 1 and RAG 2 expression go hand in hand with rearrangements of the Ig gene loci . ^^^ Moreover , the newly formed sIg+ B cells continue to express RAG 1 and RAG 2 and continue to rearrange L chain gene loci , even in the absence of proliferation , in an orderly fashion , so that kappa L+ sIg+ cells can become lambda L+ sIg+ or sIg cells , whereas lambda L+ sIg+ cells can become sIg , but not kappa L+ sIg+ cells . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Cortical thymocytes that express a TCR on their surface continue to express mRNA for the recombination activating genes RAG 1 and RAG 2 . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
By contrast , we did not detect transcripts of the RAG 1 and RAG 2 genes , which are required for 5 ( D ) J recombination at gene loci for immunoglobulin and T cell receptors . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Expression of human recombination activating genes ( RAG 1 and RAG 2 ) in angioimmunoblastic lymphadenopathy and anaplastic large cell lymphoma of T type . ^^^ In order to determine the genotypic maturation status of the proliferating lymphoid cells in angioimmunoblastic lymphadenopathy ( AILD ) and in anaplastic large cell lymphoma of T type ( T ALC ) , recombinase activating gene ( RAG 1 and RAG 2 ) expression was assessed in six AILD and five T ALC cases using a sensitive reverse transcriptase ( RT ) and competitive ( C ) polymerase chain reaction ( PCR ) . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Cleavage at a 5 ( D ) J recombination signal requires only RAG 1 and RAG 2 proteins and occurs in two steps . ^^^ Here we show that purified RAG 1 and RAG 2 proteins are sufficient to carry out this reaction . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
B 17 SCID mouse or in RAG 1 ( recombination activating gene 1 ) or RAG 2 deficient mice . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The disappearance of the broken DNA molecules occurs in the same developmental transition as termination of expression of the recombination activating genes , RAG 1 and RAG 2 . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
A transitional cell type has lost RAG 2 but not RAG 1 . ^^^ We have used a highly sensitive Northern blot probing technique to examine RAG 1 and RAG 2 mRNA expression in unmanipulated murine thymocytes of various developmental phenotypes sorted by flow cytometry . ^^^ We have found that neither RAG 1 nor RAG 2 are down regulated until thymocytes reach the TCRhi stage . ^^^ TCRhi , CD8+CD4+ cells have lost RAG 2 mRNA but continue to express significant levels of RAG 1 mRNA , providing molecular evidence that this cell type is transitional between the TCRlo , CD4+CD8+ and the TCRhi , CD4+CD8 , or CD 4 CD8+ phenotypes . . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Recombination activating genes Rag 1 and Rag 2 were isolated on the basis of their ability to confer 5 ( D ) J recombination activity when co expressed in fibroblasts . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
A large panel of cell lines deficient in DNA repair were tested for the ability to perform 5 ( D ) J recombination after introduction of the RAG 1 and RAG 2 genes . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The recombination activator genes RAG 1 and RAG 2 are essential for this process , termed 5 ( D ) J rearrangement . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Here we show that extracts made from a lymphoid cell line that expresses truncated forms of the Rag 1 and Rag 2 proteins have a signal cutting activity that obeys the 12 / 23 rule . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
In the first step of 5 ( D ) J recombination , the RAG 1 and RAG 2 proteins cleave DNA between a signal sequence and the adjacent coding sequence , generating a blunt signal end and a coding end with a closed hairpin structure . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The RAG 1 and RAG 2 proteins establish the 12 / 23 rule in 5 ( D ) J recombination . 5 ( D ) J recombination requires a pair of signal sequences with spacer lengths of 12 and 23 base pairs . ^^^ Cleavage by the RAG 1 AND RAG 2 proteins was previously shown to demand only a single signal sequence . ^^^ Coupled cutting at both sites requires only the RAG 1 and RAG 2 proteins , but depends on the metal ion . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The products of the recombination activating genes RAG 1 and RAG 2 are essential for activating 5 ( D ) J recombination , and thus are indispensable for the production of functional and diverse antigen receptors . ^^^ As defined previously , the core active regions of RAG 1 and RAG 2 permit the deletion of 40 % and 25 % , respectively , of well conversed sequence . ^^^ We show here that this `` dispensable ' ' region of RAG 1 is not necessary for coding joint formation or recombination of an integrated substrate , and this portion is not functionally redundant with the `` dispensable ' ' region of RAG 2 . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Recombination activating genes RAG 1 and RAG 2 , which are normally expressed during specific early stages of lymphocyte development , were expressed in not only the light chain shifting inducible lines but also in the non inducible cells . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The half life of RAG 1 protein in precursor B cells is increased in the absence of RAG 2 expression . ^^^ Site specific recombination of immunoglobulin and T cell receptor gene segments in B and T lymphocytes is dependent on the expression of two recombinant activation genes , Rag 1 and Rag 2 . ^^^ Here , we show that RAG 1 protein turnover in pre B cells depends on the expression of RAG 2 . ^^^ The apparent half life of RAG 1 protein is increased when RAG 2 is not expressed in differentiating pre B cells . . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Cleavage of 5 ( D ) J recombination signals by purified RAG 1 and RAG 2 proteins permits the dissection of DNA structure and sequence requirements . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
F3Ag DP thymocytes show a reduced expression of RAG 1 and RAG 2 compared with F3Ag+ DP cells . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Recombination activating gene 1 ( RAG 1 ) , as well as RAG 2 , are the only lymphoid specific genes required for 5 ( D ) J recombination . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Localization , interaction , and RNA binding properties of the 5 ( D ) J recombination activating proteins RAG 1 and RAG 2 . ^^^ The RAG 1 and RAG 2 gene products are indispensable for activating somatic rearrangement of antigen receptor gene segments . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The former has been rendered recombination competent by stable transfection of a genomic fragment comprising the recombination activating genes , RAG 1 and RAG 2 , along with some of their flanking sequences . ^^^ In both cell lines , recombinational activity reflects steady state levels of mRNA transcribed from the RAG 1 and RAG 2 genes . ^^^ A comparison of RAG 1 and RAG 2 mRNA levels within each cell line reveals almost identical response patterns indicating that RAG 1 and RAG 2 transcription is coordinately regulated . ^^^ Together , these results imply that the RAG containing fragment in L 4 fibroblasts carries most , if not all , control regions regulating the transcription of the RAG 1 and RAG 2 genes . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Initiation of 5 ( D ) J recombinations in a cell free system by RAG 1 and RAG 2 proteins . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
rag 1 and rag 2 : biochemistry and protein interactions . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
This ability is conferred by the recombination activating genes 1 and 2 ( RAG 1 and RAG 2 ) . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Six of 14 B SCID patients tested were found to carry a mutation of the recombinase activating gene 1 ( RAG 1 ) , RAG 2 , or both . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Purified RAG 1 and RAG 2 proteins can cleave DNA at 5 ( D ) J recombination signals . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Transcription of the gene was reduced in the rag 1 , rag 2 , rag 5 and rag 8 mutants , which are defective for the low affinity glucose permease , phosphoglucose isomerase , hexokinase , and a positive regulator of RAG 1 expression , respectively . . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Semiquantitative RT PCR analysis performed on mononuclear bone marrow cells indicated that lambda like , VpreB , Rag 1 , Rag 2 , and TdT transcripts expressed during proB cell stages were found at normal levels whereas E2A , CD 10 , Syk , Pax 5 , CD 19 , Igalpha , Igbeta , VH Cmu , and Vkappa Ckappa transcripts characteristic of later stages were severely depressed . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
It was found that co transfection of Oct2A together with an artificial recombination substrate increased the rate of 5 ( D ) J recombination by a factor of 3 . 4 in the fibroblast cell line L 4 which had been stably transfected with genomic DNA containing the rag 1 and rag 2 genes and their flanking regulatory sequences . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
However , the latter are positive for recombination activating gene ( RAG 1 and RAG 2 ) mRNA , which are only expressed in the precursor or immature T cell lineage , and also possess CD 3 epsilon mRNA in their cytoplasm , suggesting that CD 3 epsilon ( dim ) NK T cells are the precursor of 5 alpha 14 NK T cells . . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 1 mediates signal sequence recognition and recruitment of RAG 2 in 5 ( D ) J recombination . ^^^ Recent studies have demonstrated that DNA cleavage during 5 ( D ) J recombination is mediated by the RAG 1 and RAG 2 proteins . ^^^ Here , we use an in vivo one hybrid DNA binding assay to demonstrate that RAG 1 , in the absence of RAG 2 , can mediate signal recognition via the nonamer , with the heptamer acting to enhance its binding . ^^^ Localization of RAG 2 to the signal is dependent upon the presence of RAG 1 and is substantially more efficient with a 12 bp spacer signal than with a 23 bp spacer signal . . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The 5 ( D ) J recombinase subunits Rag 1 and Rag 2 mediate assembly of antigen receptor gene segments . ^^^ We studied the mechanisms of DNA recognition by Rag 1 / Rag 2 using surface plasmon resonance . ^^^ Once the Rag 1 / Rag 2 complex is engaged on the DNA , subsequent cleavage is directed by the heptamer sequence . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The establishment of a functional immune system with diverse antigen receptors is dependent on the 5 ( D ) J recombination activating gene products Rag 1 and Rag 2 . ^^^ Both Rag 1 and Rag 2 are required for the catalysis of the initial stages of 5 ( D ) J recombination . ^^^ Thus , functional disruption of either the Rag 1 or Rag 2 genes by homologous recombination , leads to immunodeficiency due to lymphoid arrest at a stage prior to the recombination of the antigen receptor loci . ^^^ The Rag deficient background has been used as a system for : the functional analysis of Rag 1 and Rag 2 ; studying the developmental functions of antigen receptors and other molecules of the immune system ; the molecular analysis of the early stages of the B and T cell lineages ; the co development of lymphocytes with stroma cells ; the identification of minor subpopulations of the developing immune system ; the involvement of lymphoid populations in the onset of pathogenesis . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Illegitimate recombinase activity promoted by the recombination activating RAG 1 and RAG 2 is assumed to be involved in the pathogenesis of the chromosomal translocations observed in lymphoid neoplasias . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
A mutant RAG 1 gene which lacks a part of the topoisomerase 1 like region and a mutant RAG 2 gene which lacks its 89 C terminal amino acids did not activate 5 ( D ) J recombination in NIH 3T3 cells . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The recombinase activation genes , RAG 1 and RAG 2 , are expressed together in immature T or B lymphocytes and possess activity to induce 5 ( D ) J rearrangement in T cell receptor ( TCR ) and Ig genes . ^^^ In this study , we have used RAG 1 and RAG 2 genes as markers of possible genetic recombination in developing murine preimplantation embryos , using the highly sensitive reverse transcriptase polymerase chain reaction ( RT PCR ) technique and in situ hybridization . ^^^ A PCR of 35 cycles disclosed expression of RAG 1 but not RAG 2 in morulae and blastocysts . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The first step of 5 ( D ) J recombination , specific cleavage at the recombination signal sequence ( RSS ) , can be carried out by the recombination activating proteins RAG 1 and RAG 2 . ^^^ RAG 1 and RAG 2 alone or in combination were unable to generate signal joints . ^^^ However , RAG 1 and RAG 2 complemented with nuclear extracts were able to recombine an extrachromosomal substrate and form precise signal joints . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Upon differentiation , proliferation ceases , and upregulation of Rag 1 and Rag 2 expression , and induction of 5 ( D ) J immunoglobulin gene rearrangements occur . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Reexpression of RAG 1 and RAG 2 genes in activated mature mouse B cells . ^^^ Recombination activating genes ( RAG 1 and RAG 2 ) , involved in 5 ( D ) J rearrangement of immunoglobulin genes , have been thought to be expressed only in immature stages of B cell development . ^^^ However , RAG 1 and RAG 2 transcripts were found to be reexpressed in mature mouse B cells after culture with interleukin 4 in association with several different co stimuli . ^^^ RAG 1 and RAG 2 proteins could be detected by immunofluorescence microscopy in the nuclei of B cells cultured in vitro and in the germinal centers of draining lymph nodes . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Neoteny in lymphocytes : Rag 1 and Rag 2 expression in germinal center B cells . ^^^ The products of the Rag 1 and Rag 2 genes drive genomic 5 ( D ) J rearrangements that assemble functional immunoglobulin and T cell antigen receptor genes . ^^^ Abundant RAG 1 and RAG 2 protein and messenger RNA was detected in the activated B cells that populate murine splenic and Peyer ' s patch germinal centers . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Interestingly , both RAG 1 and RAG 2 transcripts were also detected in this cell fraction , suggesting that sterile TCR transcription might be dependent upon the presence of a functional recombinase system . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The mRNA of RAG 1 , RAG 2 , Ku 80 , and terminal deoxynucleotidyl transferase ( TdT ) genes was equally detected between control and mutant thymi , suggesting that the expression of common recombination machinery is not affected . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Recent insights into the mechanism of 5 ( D ) J recombination have clarified the direct role of the products of the recombination activating genes Rag 1 and Rag 2 in site specific DNA cleavage at recombination signal sequences and have identified components of the general DNA double strand break repair pathway that participate in the rejoining of the Rag 1 and Rag 2 cut receptor gene segments . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Recent experiments have shown that cleavage is catalyzed by the RAG 1 and RAG 2 proteins and generates an asymmetric set of broken ends : hairpin coding ends and blunt signal ends . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 in developing rabbit appendix subpopulations . ^^^ We found that the CD43+IgM and double negative CD 43 IgM cells contained RAG 1 transcripts and RAG 2 protein . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 1 , RAG 2 and pre T cell receptor alpha chain expression by adult human hepatic T cells : evidence for extrathymic T cell maturation . ^^^ These were examined for molecular evidence of local T cell maturation using reverse transcription polymerase chain reaction to detect expression of recombination activation gene 1 ( RAG 1 ) , RAG 2 and pre T cell receptor alpha chain ( pTalpha ) , which occurs only in early thymocyte development . ^^^ Four specimens of whole liver were positive for RAG 1 and RAG 2 expression , whereas peripheral blood mononuclear cells from the same individuals were negative . ^^^ We detected the expression of RAG 1 , RAG 2 and pre TCRalpha in five specimens of hepatic CD2+CD7+ but not in CD45RO+ hepatic lymphocytes . ^^^ Four out of six specimens of CD2+CD7+ cells from the peripheral blood were negative for RAG 1 and RAG 2 while all six specimens were positive for pTalpha expression . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The proteins RAG 1 and RAG 2 are essential for initiation of 5 ( D ) J recombination . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
A transient 5 ( D ) J recombination assay after the introduction of the RAG 1 and RAG 2 genes indicated that the 5 ( D ) J recombination ability of the CHO irs 20 cells was about 10 % of that for the CHO wild type cells for signal join formation with an 80 % joining fidelity and only 3 % of the parental level for coding join formation . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
IL 7 did not change the m RNA levels of the 5 ( D ) J recombination activating genes RAG 1 and RAG 2 , therefore IL 7 must exert its influence on 5 ( D ) J recombination either by post transcriptional regulation of the RAG genes or by the regulation of other genes that are involved in 5 ( D ) J recombination . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The RAG 1 and RAG 2 proteins initiate 5 ( D ) J recombination by making specific double strand DNA breaks at recombination signal sequences . ^^^ We show here that RAG 1 and RAG 2 bind specifically to this sequence , forming a stable protein DNA complex . ^^^ The complex requires the conserved heptamer and nonamer motifs of the recombination signal as well as both the RAG 1 and RAG 2 proteins . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Expression of the recombinase activating genes RAG 1 and RAG 2 was greatly reduced in the IL 7R alpha / thymuses , and in DN thymocytes from the TCR transgenic IL 7R alpha / mice , but was restored in double positive thymocytes from the TCR transgenic IL 7R alpha / mice . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Definition of a large region of RAG 1 that is important for coimmunoprecipitation of RAG 2 . ^^^ Interaction between the RAG 1 and RAG 2 proteins is probably critical for 5 ( D ) J recombination . ^^^ Using a coimmunoprecipitation assay , we define a large region of RAG 1 ( amino acids 504 1008 ) that is sufficient for interaction with RAG 2 . ^^^ Deletion of either of two regions of RAG 1 ( amino acids 504 570 or 850 1008 ) causes a loss of interaction with RAG 2 . ^^^ Loss of coimmunoprecipitation is also seen with RAG 1 core proteins containing deletions of smaller stretches of amino acids ( amino acids 506 511 or 545 550 ) , emphasizing the importance of this region of RAG 1 in forming a complex with RAG 2 . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
To follow development of the immune system in zebrafish , we have analyzed the expression of the recombination activating genes , rag 1 and rag 2 , which we have previously isolated and characterized . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Truncated RAG 1 and RAG 2 proteins , while capable of cleaving at isolated RSS in cell free systems , also require a 12 / 23 RSS pair for efficient cleavage in vivo . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Characterization and expression of the recombination activating genes ( rag 1 and rag 2 ) of zebrafish . ^^^ The closely linked recombination activating genes , rag 1 and rag 2 , encode components of the recombinase involved in 5 ( D ) J recombination of the immunoglobulin and T cell receptor genes . ^^^ We cloned the rag locus of the zebrafish Danio rerio and sequenced the open reading frames of the rag 1 and rag 2 genes . ^^^ Expression of both rag 1 and rag 2 begins late in embryonic development , on day 4 , by northern RNA blot analysis . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 form a stable postcleavage synaptic complex with DNA containing signal ends in 5 ( D ) J recombination . ^^^ During 5 ( D ) J recombination , RAG 1 and RAG 2 cleave DNA adjacent to highly conserved recombination signals , but nothing is known about the protein DNA complexes that exist after cleavage . ^^^ This complex includes the proteins RAG 1 , RAG 2 , HMG 1 or the closely related HMG 2 protein , and the components of the DNA dependent protein kinase . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
In three independently derived mouse strains lacking the recombination activating genes RAG 1 or RAG 2 , which are essential for Ig production , Ig ir was absent from the fetal CNS . ^^^ Western blot analyses of wild type brains from embryonic day 12 through birth identified a 25 kDa protein that co migrated with Ig light chain and was absent from RAG 1 or RAG 2 / brain samples . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
New work shows that the first step is a site specific cleavage which can be performed by purified RAG 1 and RAG 2 proteins . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The first stage of the reaction , which can be reproduced with the purified RAG 1 and RAG 2 proteins , is a site specific cleavage that generates the same broken DNA species found in vivo . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Products of recombination activating genes ( RAG 1 and RAG 2 ) involved in the rearrangement of Ig genes have been shown to be expressed only in immature stages of B cells . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
A complex of RAG 1 and RAG 2 proteins persists on DNA after single strand cleavage at 5 ( D ) J recombination signal sequences . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
V ( D ) J recombination : modulation of RAG 1 and RAG 2 cleavage activity on 12 / 23 substrates by whole cell extract and DNA bending proteins . ^^^ Recent studies have shown that this restriction operates at the level of DNA cleavage , which is mediated by the products of the recombination activating genes RAG 1 and RAG 2 . ^^^ Here , we show that RAG 1 and RAG 2 are not sufficient for 12 / 23 dependent cleavage , whereas RAG 1 and RAG 2 complemented with whole cell extract faithfully recapitulates the 12 / 23 rule . ^^^ In addition , HMG box containing proteins HMG 1 and HMG 2 enhance RAG 1 and RAG 2 mediated cleavage of substrates containing 23 RSS but not of substrates containing only 12 RSS . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Farage cells did not express the terminal deoxynucleotydyl transferase gene ( TdT ) , nor the recombination activating genes RAG 1 and RAG 2 , known as markers of the pre B cell stage . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The RAG 1 and RAG 2 proteins initiate the reaction by making double strand DNA breaks at both signals , and must thus be able to operate on these two different spatial arrangements . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 genes are transcriptionally active in fetal and adult IL 7R alpha / thymocytes . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
It is now clear that the RAG 1 and RAG 2 proteins play a direct role in DNA recognition and cleavage and that both RAG proteins are required for the nicking and strand transfer steps of the cleavage reaction . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Proteins encoded by the RAG 1 and RAG 2 genes are responsible for the recognition and double stranded cleavage of a highly conserved DNA sequence flanking all rearranging gene segments . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The end joining reaction in 5 ( D ) J recombination . 5 ( D ) J recombination consists of a DNA cleavage reaction catalysed by RAG 1 and RAG 2 , followed by an end joining reaction that utilizes the cell ' s double strand break repair machinery . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Furthermore , the Ku 70 ( / ) cells lack the ability to effectively rejoin signal and coding ends liberated in transiently introduced 5 ( D ) J recombination substrates by enforced RAG 1 and RAG 2 expression . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Semi quantitative RT PCR analysis performed on mononuclear bone marrow cells from the non XLA patient indicated that lambda like , VpreB , Rag 1 , Rag 2 and TdT transcripts expressed during proB cell stages were found at normal levels whereas E2A , CD 10 , Syk , Pax 5 , CD 19 , Ig alpha , Ig beta , VH C mu and 5 kappa C kappa transcripts characteristic of later stages were severely depressed . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The RAG 1 and RAG 2 proteins are the critical lymphoid cell specific components of the recombination enzymatic machinery and are responsible for site specific DNA recognition and cleavage . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The first step in DNA cleavage at 5 ( D ) J recombination signals by RAG 1 and RAG 2 is creation of a nick at the heptamer / coding flank border . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
In vitro coding joint formation requires RAG 1 , RAG 2 , and heat labile factors present in the nuclear extract of nonlymphoid cells . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 dependent assembly of functional complexes with 5 ( D ) J recombination substrates in solution . 5 ( D ) J recombination is initiated by RAG 1 and RAG 2 , which introduce double strand DNA breaks at recombination signal sequences ( RSSs ) of antigen receptor gene segments to produce signal ends , terminating in blunt , double strand breaks , and coding ends , terminating in DNA hairpins . ^^^ While the formation of RAG RSS complexes has been documented , observations regarding the individual contributions of RAG 1 and RAG 2 to RSS recognition are in conflict . ^^^ Notably , the presence of both RAG 1 and RAG 2 is essential for formation of stable , functional complexes with substrate DNA under conditions of the sequestration assay . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Hence , it became obvious that the initial steps of the reaction are carried out by the lymphocyte specific proteins RAG 1 and RAG 2 ( recombination activating genes ) , with the help of members of the high mobility group protein family of DNA binding proteins , HMG 1 or HMG 2 . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Cloning and characterization of the human recombination activating gene 1 ( RAG 1 ) and RAG 2 promoter regions . ^^^ Recombination activating gene 1 ( RAG 1 ) and RAG 2 are the essential and tissue specific components of 5 ( D ) J recombination . ^^^ We have characterized the genomic organization of the human RAG locus , mapped the transcriptional initiation sites , and partially sequenced and performed functional reporter assays on the 5 ' flanking regions of human RAG 1 and RAG 2 . ^^^ The 5 ' flanking region of the human RAG 2 gene is TATA less ; however , there is a GATAA consensus at position 34 with respect to the major transcriptional initiation site of RAG 1 . ^^^ Promoter regions of human RAG 1 and RAG 2 are active in both lymphoid and nonlymphoid cell lines , suggesting that an outside regulatory element is probably involved in the tissue specific transcriptional regulation of the RAG genes . . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Rag 1 and Rag 2 are required for the somatic rearrangement of immunoglobulin genes and T cell receptor genes and the subsequent development of B and T cells . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
To examine whether the development of thymic lymphoma in p 53 / mice was dependent on the process of 5 ( D ) J recombination , we generated p 53 / mice that were also mutant for the Rag 1 or Rag 2 genes . ^^^ Both Rag 1 / ; p 53 / and Rag 2 / ; p 53 / mice developed thymic lymphoma at high frequency , and the tumors arose with short latency . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Rejoining of DNA by the RAG 1 and RAG 2 proteins . ^^^ Assembly of immunoglobulin and T cell receptor genes from separate gene segments [ 5 ( D ) J recombination ] begins with DNA double strand breakage by the RAG 1 and RAG 2 proteins , acting at a pair of recombination signal sequences ( RSSs ) . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RT PCR revealed that TCDD reduced RAG 1 , RAG 2 , and TdT gene expression in the CD 4 CD8 double negative thymocytes . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
To investigate potential roles of the RAG 1 and RAG 2 gene products in Ig heavy chain class recombination ( CSR ) , we have generated RAG 1 ( / ) and RAG 2 ( / ) mice which contain both a rearranged Ig HC 5 ( D ) J gene ( referred to as B 1 8 ) inserted into the endogenous Ig heavy chain ( HC ) locus in place of the JH segments , and a rearranged lambda 1 light chain ( LC ) transgene ( which are referred to as RAG 1 ( / ) B 1 8lambda and RAG 2 ( / ) B 1 8lambda mice respectively ) . ^^^ The B 1 8 HC gene and lambda LC genes encode proteins that associate to form a complete Ig molecule , the expression of which leads to substantial reconstitution of the peripheral B cell compartments of RAG 1 ( / ) B 1 8lambda and RAG 2 ( / ) B 1 8lambda mice . ^^^ Both RAG 1 ( / ) B 1 8lambda and RAG 2 ( / ) B 1 8lambda mice have relatively normal levels of the various IgG isotypes , but greatly reduced levels of serum IgM and IgA compared to normal littermates . ^^^ Furthermore , RAG 1 ( / ) B 1 8lambda and RAG 2 ( / ) B 1 8lambda B cells activated in vitro with lipopolysaccharide ( LPS ) or LPS plus IL 4 responded similarly to control B cells with respect to surface expression and secretion of IgG 3 , IgG 1 , IgG2b , IgG2a and IgE , but again were deficient in the secretion of IgM . ^^^ Together , these findings indicate that neither RAG 1 nor RAG 2 expression is required for efficient class switching to most HC isotypes in B cells . . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Recombination activating gene ( RAG ) deficiencies were introduced into both p 53 / mice and TgTDeltaN transgenic mice , a strain in which 100 % of the mice develop thymoma due to thymocyte specific inactivation of p 53 by a simian virus 40 T antigen variant . 5 ( D ) J recombination was dispensable for tumorigenesis since thymomas developed with or without the RAG 1 or RAG 2 gene , although some delay was observed . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Inspection of the 3 ' UTR genomic region for RAG 1 and RAG 2 in rainbow trout ( Oncorhynchus mykiss ) reveals potential regulatory motifs . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Lack of expression of the recombination activating genes RAG 1 and RAG 2 in cutaneous T cell lymphoma : pathogenic implications . ^^^ To study whether illegitimate 5 ( D ) J recombination is responsible for the continuously increasing number of DNA breaks in CTCL , we used reverse transcriptase polymerase chain reaction ( RT PCR ) to analyse three CTCL cell lines and biopsies from 14 CTCL patients for the expression of the RAG 1 and RAG 2 genes which are essential for 5 ( D ) J recombination . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
In contrast to 5 ( D ) J recombination , which is mediated by RAG 1 , RAG 2 and DNA double stranded break ( DSB ) repair proteins , little is known about the mechanism of switching . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Genomic rearrangement of the antigen receptor loci is initiated by the two lymphoid specific proteins Rag 1 and Rag 2 . ^^^ We report here that patients with Omenn syndrome , a severe immunodeficiency characterized by the presence of activated , anergic , oligoclonal T cells , hypereosinophilia , and high IgE levels , bear missense mutations in either the Rag 1 or Rag 2 genes that result in partial activity of the two proteins . ^^^ Two of the amino acid substitutions map within the Rag 1 homeodomain and decrease DNA binding activity , while three others lower the efficiency of Rag 1 / Rag 2 interaction . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
This process is initiated by the recombination activating proteins RAG 1 and RAG 2 , which recognize the recombination signal sequences ( RSS ) and cleave the DNA at the coding / RSS junction . ^^^ In this study , we show that RAG 1 and RAG 2 have the ability to directly interact in solution before binding to the DNA . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Recombination activating genes , RAG 1 and RAG 2 , encode proteins that catalyze the rearrangement of immunoglobulin genes in B cells and T cell receptor genes in T cells to generate the diversity of these important recognition molecules in immune system . ^^^ However , recent studies have revealed that even mature B cells in peripheral lymphoid tissues can reexpress RAG 1 and RAG 2 proteins following immunization . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The adult thymus has multiple defects , including reduced cell numbers and proportions of the more mature thymocyte subsets , a complete absence of CD25+ cells and a reduced level of RAG 1 and RAG 2 expression . ^^^ Moreover , normal levels of RAG 1 and RAG 2 were observed . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The site specific recombination of antigen receptor gene segments in T and B lymphocytes is dependent on the expression of two recombination activating genes , RAG 1 and RAG 2 . ^^^ The RAG 1 and RAG 2 proteins are essential for the cleavage of DNA at highly conserved recombination signals to make double strand breaks and their expression is sufficient to confer 5 ( D ) J recombination activity to non lymphoid cells . ^^^ However , several laboratories have now demonstrated expression of RAG 1 and RAG 2 and active 5 to ( D ) J recombination in germinal center B cells . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Expression of CD 3 epsilon , CD 3 zeta , and RAG 1 / RAG 2 in decidual CD56+ NK cells . ^^^ In contrast to previous reports , there was no evidence of RAG 1 nor RAG 2 expression in decidual NK cells . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
In the studies reported here , the authors have analysed cytokine / growth factor gene expression , recombinase activating gene RAG 1 and RAG 2 gene expression and terminal deoxynucleotidyl transferase ( TdT ) gene expression in mouse fetal intestine and fetal thymus and liver , two known haematopoietic tissues . ^^^ RAG 1 and RAG 2 mRNA was detected in all three fetal tissues . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Rag 1 and Rag 2 are the critical components of the 5 ( D ) J recombinase required for site specific recombination of the antigen receptor genes . ^^^ In this study , we have examined the ability of recombinant ( r ) Rag 1 and Rag 2 to bind the recombination signal sequences ( RSS ) and have determined that rRag 1 , but not rRag 2 , is able to directly bind DNA . rRAG 1 DNA binding activity was found to reside within a novel amino terminal arginine rich ( RR ) domain with partial homology to a variety of nucleic acid binding domains . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Recombination is initiated by the RAG 1 and RAG 2 proteins , which introduce double stranded DNA breaks ( DSB ) adjacent to the Ig and TCR gene segments . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
V ( D ) J recombination signal recognition : distinct , overlapping DNA protein contacts in complexes containing RAG 1 with and without RAG 2 . ^^^ Protein interactions with 5 ( D ) J recombination signal sequences ( RSSs ) were mapped in complexes containing RAG 1 with ( M1 / 2 ) or without ( M 1 ) RAG 2 . ^^^ Thus , while RAG 1 alone can bind the nonamer , RAG 2 is required for heptamer occupancy . . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Because a common 5 ( D ) J recombinase comprising RAG 1 and RAG 2 proteins is used for both B and T cell antigen receptor assembly , lineage specific rearrangement must be modulated through differential access to sites of recombination . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The RAG 1 and RAG 2 proteins , as well as the DNA bending protein HMG 1 , are needed for efficient formation of this complex . ^^^ After cleavage , all four broken DNA ends remain associated with the RAG proteins in a postcleavage synaptic complex , whose existence helps to explain the known role of RAG 1 and RAG 2 in the subsequent end joining events that complete 5 ( D ) J recombination . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Distinct roles of RAG 1 and RAG 2 in binding the 5 ( D ) J recombination signal sequences . ^^^ The RAG 1 and RAG 2 proteins initiate 5 ( D ) J recombination by introducing double strand breaks at the border between a recombination signal sequence ( RSS ) and a coding segment . ^^^ To understand the distinct functions of RAG 1 and RAG 2 in signal recognition , we have compared the DNA binding activities of RAG 1 alone and RAG 1 plus RAG 2 by gel retardation and footprinting analyses . ^^^ Although direct binding of RAG 2 by itself was not detected , the presence of both RAG 1 and RAG 2 results in the formation of a RAG 1 RAG2 DNA complex which is more stable and more specific than the RAG 1 DNA complex and is active in 5 ( D ) J cleavage . ^^^ These results suggest that biologically effective discrimination between an RSS and nonspecific sequences requires both RAG 1 and RAG 2 . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Cleavage in vitro by the RAG 1 and RAG 2 proteins can occur at individual signals when the reaction buffer contains Mn2+ , but cleavage is restricted to substrates containing two signals when Mg2+ is the divalent cation . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The RAG 1 and RAG 2 proteins play a crucial role in 5 ( D ) J recombination by cooperating to make specific double stranded DNA breaks at a pair of recombination signal sequences ( RSSs ) . ^^^ Given the known properties of the beta propeller fold in mediating protein protein interactions , it is proposed that this six laded propeller structure of the RAG 2 active core would play a crucial role in the tight complex formed by the RAG 1 and RAG 2 proteins and RSSs . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Under physiologic conditions , we found that the complex of RAG 1 , RAG 2 , and HMG 1 can successfully recapitulate the 12 / 23 rule with the same specificity as that seen intracellularly and in crude extracts . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Re expression of RAG 1 and RAG 2 genes and evidence for secondary rearrangements in human germinal center B lymphocytes . 5 ( D ) J recombination occurs in immature B cells within primary lymphoid organs . ^^^ However , recent evidence demonstrated that the recombination activating genes RAG 1 and RAG 2 can also be expressed in murine germinal centers ( GC ) where they can mediate secondary rearrangements . ^^^ In the present report , we provide evidence that human GC B cells that have lost surface immunoglobulin re express RAG 1 and RAG 2 , suggesting that they may be able to undergo Ig rearrangement . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Checkpoints in thymocytopoiesis in aging : expression of the recombination activating genes RAG 1 and RAG 2 . ^^^ We examined the expression of recombinase activating genes , RAG 1 and RAG 2 , in the thymus of mice at different ages ( 2 24 months ) . ^^^ A significant age related decrease in RAG 1 and RAG 2 expression was observed in the thymocytes from the age of 12 months and over . ^^^ Whereas cells derived from the immature thymocytes of the old donors failed to express RAG 1 and RAG 2 , compared to the young , the bone marrow derived cells of both age groups did show this expression , and there was no difference in Vbeta rearrangement of the TCR . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Transposition mediated by RAG 1 and RAG 2 and its implications for the evolution of the immune system . ^^^ The proteins encoded by the recombination activating genes , RAG 1 and RAG 2 , are essential in this reaction , mediating sequence specific DNA recognition of well defined recombination signals and DNA cleavage next to these signals . ^^^ Here we show that RAG 1 and RAG 2 together form a transposase capable of excising a piece of DNA containing recombination signals from a donor site and inserting it into a target DNA molecule . ^^^ The results support the theory that RAG 1 and RAG 2 were once components of a transposable element , and that the split nature of immunoglobulin and T cell receptor genes derives from germline insertion of this element into an ancestral receptor gene soon after the evolutionary divergence of jawed and jawless vertebrates . . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
DNA transposition by the RAG 1 and RAG 2 proteins : a possible source of oncogenic translocations . ^^^ The RAG 1 and RAG 2 proteins are known to initiate 5 ( D ) J recombination by making a double strand break between the recombination signal sequence ( RSS ) and the neighboring coding DNA . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
In striking contrast to the plasma cell phenotype , recombination activating genes , RAG 1 and RAG 2 , were expressed in the HTD 8 cells and were shown to be necessary , but insufficient for inducing expression of the new lambda chain . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Similar to the effects of an immunoglobulin ( Ig ) mu heavy chain ( HC ) transgene , activated Ras caused progression of RAG 1 deficient progenitor ( pro ) B cells to cells that shared many characteristics with precursor ( pre ) B cells , including downregulation of surface CD 43 expression plus expression of lambda 5 , RAG 2 , and germline kappa locus transcripts . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Hairpin coding end opening is mediated by RAG 1 and RAG 2 proteins . ^^^ Here , we show that RAG 1 plus RAG 2 can open DNA hairpins . ^^^ Mutations in either RAG 1 or RAG 2 that interfere with RSS cleavage also interfere with hairpin opening , suggesting that RAGs have a single active site that catalyzes several distinct DNA cleavage reactions . . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Peripheral CD4+ T cells reexpress the recombination activating genes , RAG 1 and RAG 2 , and contain signal end intermediates indicative of ongoing 5 ( D ) J recombination . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Sequence of the rag 1 and rag 2 intergenic region in zebrafish ( Danio rerio ) . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The recombination activating genes RAG 1 and RAG 2 are highly conserved throughout evolution and are necessary and essential for the DNA rearrangement of antigen receptor gene segments . ^^^ Experiments with a mouse fibroblast line stably transfected with a genomic fragment of the RAG locus suggest that the intergenic region between RAG 1 and RAG 2 may contain information modulating RAG transcription . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Here we show that B 1 cells , like germinal centre B cells , can express recombinase activating genes 1 and 2 ( RAG 1 and RAG 2 ) and undergo secondary 5 ( D ) J recombination of immunoglobulin genes . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Both B 220 ( ) and B 220 ( + ) cells similarly express the IgH germ line transcript ( Imu ) , mRNAs for recombinase ( TdT , Rag 1 , and Rag 2 ) , and lymphoid specific transcription factors ( Pax 5 , EBF , E12 / E47 , Oct 2 , and Ikaros ) , but the DNA binding activity of Pax 5 , EBF , Oct 2 , and E2A are low in B 220 ( ) cells and while high in B 220 ( + ) cells . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 cooperate in specific binding to the recombination signal sequence in vitro . ^^^ This process , termed `` 5 ( D ) J recombination , ' ' begins with DNA cleavage at the appropriate sites mediated by the two proteins RAG 1 and RAG 2 . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The recombination activating genes RAG 1 and RAG 2 are expressed in a lymphoid cell specific and developmentally regulated fashion . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 2 promotes heptamer occupancy by RAG 1 in the assembly of a 5 ( D ) J initiation complex . 5 ( D ) J recombination occurs at recombination signal sequences ( RSSs ) containing conserved heptamer and nonamer elements . ^^^ RAG 1 and RAG 2 initiate recombination by cleaving DNA between heptamers and antigen receptor coding segments . ^^^ RAG 2 by itself has no DNA binding activity but promotes heptamer occupancy in the presence of RAG 1 ; how RAG 2 collaborates with RAG 1 has been poorly understood . ^^^ Here we examine the composition of RAG RSS complexes and the relative contributions of RAG 1 and RAG 2 to heptamer binding . ^^^ RAG 1 exists as a dimer in complexes with an isolated RSS bearing a 12 bp spacer , regardless of whether RAG 2 is present ; only a single subunit of RAG 1 , however , participates in nonamer binding . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
DNA cleavage is mediated by the RAG 1 and RAG 2 proteins . ^^^ We also detect cross linking of RAG 2 protein to some of the same nucleotides that cross link to RAG 1 , indicating that , in the binding complex , both RAG proteins are in close proximity to the site of cleavage . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Omenn syndrome : a disorder of Rag 1 and Rag 2 genes . ^^^ This process , known as 5 ( D ) J recombination , is initiated by the lymphoid specific proteins Rag 1 and Rag 2 . ^^^ Both in humans and in animal models , mutations that abrogate expression of either the Rag 1 or Rag 2 proteins result in severe combined immune deficiency with a complete lack of circulating T and B cells due to an early block in lymphoid development . ^^^ We have recently shown that mutations that impair , but do not completely abolish the function of Rag 1 and Rag 2 in humans result in Omenn syndrome , an enigmatic form of combined immune deficiency characterized by oligoclonal , activated T lymphocytes with a skewed Th 2 profile . . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
DNA hairpin opening mediated by the RAG 1 and RAG 2 proteins . ^^^ The lymphoid cell specific proteins RAG 1 and RAG 2 initiate 5 ( D ) J recombination by cleaving DNA adjacent to recombination signals , generating blunt signal ends and covalently sealed , hairpin coding ends . ^^^ Here we demonstrate that RAG 1 and RAG 2 possess an intrinsic single stranded nuclease activity capable of nicking hairpin coding ends at or near the hairpin tip . ^^^ RAG 1 and RAG 2 may therefore be responsible for initiating the processing of coding ends and for the generation of P nucleotides during 5 ( D ) J recombination . . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Roles of the `` dispensable ' ' portions of RAG 1 and RAG 2 in 5 ( D ) J recombination . 5 ( D ) J recombination is initiated by introduction of site specific double stranded DNA breaks by the RAG 1 and RAG 2 proteins . ^^^ It is not known whether truncating RAG 1 and / or RAG 2 affects the cleavage step or the joining step of recombination . ^^^ Furthermore , we found that removal of portions of the dispensable regions of RAG 1 and RAG 2 affects the efficiency of product formation without altering the levels of recombination intermediates . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 are the two lymphoid specific proteins required for the cleavage of DNA sequences known as the recombination signal sequences ( RSSs ) flanking 5 , D or J regions of the antigen binding genes . ^^^ Previous studies have shown that RAG 1 alone is capable of binding to the RSS , whereas RAG 2 only binds as a RAG1 / RAG2 complex . ^^^ We have expressed recombinant core RAG 1 ( amino acids 384 1008 ) in Escherichia coli and demonstrated catalytic activity when combined with RAG 2 . ^^^ The purified RAG 1 protein overexpressed in E . coli exhibited the expected cleavage activity when combined with RAG 2 purified from transfected 293T cells . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
In this report , we investigated the basis of this regulation by testing the ability of purified RAG 1 and RAG 2 proteins to initiate cleavage on positioned nucleosomes containing RSS substrates . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
HB4C5 is a human antibody producing plasma B cell line that expresses the recombination activating gene 1 ( RAG 1 ) and RAG 2 constitutively , but undergoes few secondary immunoglobulin gene rearrangements when cultured in fetal bovine serum containing medium . ^^^ To investigate the induction mechanism of secondary VlambdaJlambda rearrangement , we assessed the expression levels of RAG 1 and RAG 2 products , Vlambda germline transcription level and the amount of Vlambda signal broken ends ( SBE ) in HB4C5 cells cultured in serum supplemented or serum free medium . ^^^ Western blot analysis showed that the expression level for the RAG 1 and RAG 2 proteins was not affected by the serum depletion . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The steady state level of both RAG 1 and RAG 2 mRNA , the number of Pre B cells , and the number of Pre B cells expressing RAG 2 protein decrease in the bone marrow of old mice . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
A RAG 1 and RAG 2 tetramer complex is active in cleavage in 5 ( D ) J recombination . ^^^ During 5 ( D ) J recombination two proteins , RAG 1 and RAG 2 , assemble as a protein DNA complex with the appropriate DNA targets containing recombination signal sequences ( RSSs ) . ^^^ The coexpressed RAG 1 and RAG 2 proteins form a mixed tetramer in solution which contains two molecules of each protein . ^^^ The same tetramer of RAG 1 and RAG 2 plus one DNA molecule is the form active in cleavage . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Pro B cells from Ebf+ / E2a+ / mice show reduced expression of lymphoid specific transcripts , including Pax 5 , Rag 1 , Rag 2 , and mb 1 . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Coordinate regulation of RAG 1 and RAG 2 by cell type specific DNA elements 5 ' of RAG 2 . ^^^ RAG 1 and RAG 2 are essential for 5 ( D ) J recombination and lymphocyte development . ^^^ The regulation of RAG 1 and RAG 2 was investigated in vivo with bacterial artificial chromosome ( BAC ) transgenes containing a fluorescent indicator . ^^^ Coordinate expression of RAG 1 and RAG 2 in B and T cells was found to be regulated by distinct genetic elements found on the 5 ' side of the RAG 2 gene . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Some mutations that alter the amino acid sequence of RAG 1 or RAG 2 have been shown to disturb B cell generation and to partially disturb T cell generation , resulting in Omenn syndrome in humans ; moreover , peripheral re expression of RAGs indicates their role in lymphoid cell homeostasis . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
We have previously identified a DDE like region in the RAG 2 protein and a similar region within the RAG 1 protein . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 proteins cleave precisely at the RSS coding sequence border leading to flush signal ends and coding ends with a hairpin structure ( Eastman , M . , Leu , T . , Schatz , D . , 1996 . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Transposition mediated by RAG 1 and RAG 2 and the evolution of the adaptive immune system . ^^^ The RAG 1 and RAG 2 proteins together initiate 5 ( D ) J recombination by performing cleavage of chromosomal DNA adjacent to antigen receptor gene segments . ^^^ Like the adaptive immune system itself , RAG 1 and RAG 2 are found only in jawed vertebrates . ^^^ The hypothesis that RAG 1 and RAG 2 arose in evolution as components of a transposable element has received dramatic support from our recent finding that the RAG proteins are a fully functional transposase in vitro . ^^^ This result strongly suggests that antigen receptor genes acquired their unusual structure as a consequence of the insertion of a transposable element into an ancestral receptor gene by RAG 1 and RAG 2 approx 450 million years ago . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Moreover , the expression of genes encoding components of the rearrangement machinery ( RAG 1 , RAG 2 , TdT ) or pre B cell receptor ( lambda 5 , VpreB , Igalpha , Igbeta ) has been considered to indicate B lineage commitment . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The 5 ( D ) J recombination reaction is directed by a recombinase complex from the RAG 1 and RAG 2 genes , and is modulated by several other gene products . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
We addressed whether this was related to their immunodeficiency by similarly treating Rag 1 ( / ) and Rag 2 ( / ) knockout mice which also lack mature T and B lymphocytes . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Mutational analysis of RAG 1 and RAG 2 identifies three catalytic amino acids in RAG 1 critical for both cleavage steps of 5 ( D ) J recombination . ^^^ RAG 1 and RAG 2 initiate 5 ( D ) J recombination , the process of rearranging the antigen binding domain of immunoglobulins and T cell receptors , by introducing site specific double strand breaks ( DSB ) in chromosomal DNA during lymphocyte development . ^^^ We altered each conserved acidic amino acid in RAG 1 and RAG 2 by site directed mutagenesis , and examined > 100 mutants using a combination of in vivo and in vitro analyses . ^^^ No conserved acidic amino acids in RAG 2 were critical for catalysis ; three RAG 1 mutants retained normal DNA binding , but were catalytically inactive for both nicking and hairpin formation . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The RAG 1 and RAG 2 proteins collaborate to initiate 5 ( D ) J recombination by binding recombination signal sequences ( RSSs ) and making a double strand break between the RSS and adjacent coding DNA . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Omenn syndrome was recently found to be caused by missense mutations in RAG 1 or RAG 2 gene that result in partial 5 ( D ) J recombination activity . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
In contrast , the generation of pre pro B cells and pro B cells appeared to be normal , as judged by total cell numbers , proliferative indexes , D JH and 5 DJH gene rearrangements , and mRNA for recombinase activating gene 1 ( RAG 1 ) , RAG 2 , TdT , Ig mu , lambda 5 , and VpreB . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
In addition to RAG 1 and RAG 2 , the protein HMG 1 is known to stimulate the efficiency of the cleavage reaction . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
During 5 ( D ) J recombination , the RAG 1 and RAG 2 proteins cooperate to catalyze a series of DNA bond breakage and strand transfer reactions . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Although the plasma cells used express both RAG 1 and RAG 2 , the expression level of these proteins was not affected by caffeine or okadaic acid . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The process of antigen receptor gene rearrangement , 5 ( D ) J recombination , involves DNA cleavage by the RAG 1 and RAG 2 proteins . ^^^ To test this hypothesis , we constructed mutant versions of RAG 1 and RAG 2 in which all four DNA PK consensus phosphorylation sites were removed by site directed mutagenesis . ^^^ |
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Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Mutations were detected in the probands as well as in their parents by genomic sequencing of the complete coding regions of both RAG 1 and RAG 2 , which are contained in a single exon . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The recombinase activating genes , RAG 1 and RAG 2 , can be expressed by a subset of B cells within germinal centers , where they mediate secondary 5 ( D ) J rearrangements . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The recombinase activating genes ( RAG 1 and RAG 2 ) encode nuclear proteins that directly mediate the mechanism 5 ( D ) J recombination process that occurs in T and B lymphocytes . ^^^ The expression of RAG 1 and RAG 2 is required for the proper development of maturing lymphocytes . ^^^ We found three complete genes , RAG 1 , RAG 2 and ACS ( a possible homologue of the plant 1 aminocyclopropane carboxylate synthase gene ) . ^^^ The genetic structure of both RAG 1 and RAG 2 is identical to that found in other fish , but the size of the intergenic region is smaller in Fugu . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Here we report that the high mobility group protein , HMG 1 , is necessary for the correct nicking of the 23 bp recombination signal sequence ( 23 RSS ) by the recombination [ corrected ] activating gene ( RAG ) proteins , RAG 1 and RAG 2 . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
A common recombination mechanism , initiated by the proteins RAG 1 and RAG 2 at conserved recombination signal sequences ( RSSs ) , operates at all rearranging loci [ 2 ] [ 3 ] . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
In this report , we use deletion mapping and site directed mutagenesis to determine the minimal domains critical for interaction between RAG 1 and RAG 2 . ^^^ We define the active core of RAG 2 required for RSS cleavage as aa 1 371 and demonstrate that the C terminal 57 aa of this core provide a dominant surface for RAG 1 interaction . ^^^ We also show that zinc finger B ( aa 727 750 ) of RAG 1 provides a dominant interaction domain for recruiting RAG 2 . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The RAG proteins and 5 ( D ) J recombination : complexes , ends , and transposition . 5 ( D ) J recombination proceeds through a series of protein : DNA complexes mediated in part by the RAG 1 and RAG 2 proteins . ^^^ Finally , we discuss the evolutionary and functional implications of the finding that RAG 1 and RAG 2 constitute a transposase , and we consider RAG protein biochemistry in the context of several bacterial transposition systems . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Recombination activating gene 1 ( RAG 1 ) and RAG 2 are expressed in lymphoid cells undergoing the antigen receptor gene rearrangement . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Here we show that E2A proteins act in concert with RAG 1 and RAG 2 to activate Ig VK1J but not Iglambda VlambdaIII Jlambda 1 rearrangement in an embryonic kidney cell line . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The proteins encoded by RAG 1 and RAG 2 can initiate gene recombination by site specific cleavage of DNA in immunoglobulin and T cell receptor ( TCR ) loci . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The site specific cleavage mediated by RAG 1 and RAG 2 proteins generates two types of double strand DNA breaks : blunt signal ends and covalently sealed hairpin coding ends . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Two lymphoid specific proteins , RAG 1 and RAG 2 , initiate this process at two recombination signal sequences . ^^^ RAG 1 possesses the active site of the 5 ( D ) J recombinase although RAG 2 is essential for signal binding and cleavage . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Recombination activating genes RAG 1 and RAG 2 are essential components of 5 ( D ) J recombination , a process that generates the specific antigen receptors in lymphocytes . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 expression by B cell subsets from human tonsil and peripheral blood . ^^^ Neither RAG 1 nor RAG 2 mRNA was routinely found in normal peripheral blood B cells . ^^^ In individual tonsil B cells , RAG 1 and RAG 2 mRNAs were found in 18 % of naive B cells , 22 % of GC founder cells , 0 % of centroblasts , 13 % of centrocytes , and 9 % of memory B cells . ^^^ Individual naive tonsil B cells containing both RAG 1 and RAG 2 mRNA were activated ( CD 69 ( + ) ) . ^^^ In normal peripheral blood approximately 5 % of B cells expressed both RAG 1 and RAG 2 . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
However , the expression of a heterogeneous ( T + NK or myeloid ) marker profile or of `` early ' ' antigens ( such as TdT , CD 10 , RAG 1 , RAG 2 ) render them more likely to be in the acute leukemia group . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Furthermore , we show that the lymphocyte specific endonuclease encoded by the recombinase activating genes ( RAG 1 and RAG 2 ) is required for radiation induced thymic lymphomagenesis in SCID mice . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
DNA cleavage is catalyzed by RAG 1 and RAG 2 in two chemical steps : first strand nicking , followed by hairpin formation via direct transesterification . ^^^ In vitro , these reactions minimally proceed in discrete protein DNA complexes containing dimeric RAG 1 and one or two RAG 2 monomers bound to a single recombination signal sequence . ^^^ To investigate which RAG 1 subunit contributes the residues of the DDE triad to the recombinase active site , cleavage of intact or prenicked DNA substrates was analyzed in situ in complexes containing RAG 2 and a RAG 1 heterodimer that carried an active site mutation targeted to the same or opposite RAG 1 subunit mutated to be incompetent for DNA binding . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Expression of T cell receptor and surface immunoglobulins on T and B lymphocytes , respectively , is strictly dependent on the variable , ( diversity ) joining exon ( 5 ( D ) J ) recombination process , which is initiated by the lymphoid specific recombinase activating gene proteins 1 and 2 ( RAG 1 and RAG 2 ) . ^^^ Recent advances have highlighted the functional organization of the RAG 1 and RAG 2 proteins and have provided important information on the regulation of RAG gene expression . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The only established physiological function of the 5 ( D ) J recombinase , comprising RAG 1 and RAG 2 , is to perform DNA cleavage . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Missense mutations detected in OS have been examined in a number of biochemical assays and have contributed to dissect the various functional domains of both Rag 1 and Rag 2 proteins . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Our results demonstrate that DMSO induces cell growth inhibition , cell phenotype changes , with down regulation of CD 2 and CD 7 , and increases in alpha / beta or gamma / delta TCR chains led by TdT , RAG 1 and RAG 2 activity . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Central to this reaction is the organization of the protein DNA complex containing the proteins RAG 1 and RAG 2 and their DNA targets . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Two proteins , RAG 1 and RAG 2 , together form the nuclease that cleaves the DNA at the border of the signal sequences . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Expression of the recombination activating genes ( RAG 1 and RAG 2 ) is not detectable in Epstein Barr virus associated human lymphomas . ^^^ The expression of the recombination activating genes ( RAG 1 and RAG 2 ) is largely restricted to immature lymphoid cells . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
It has been hypothesized that OR gene regulation may involve stochastic DNA rearrangement , which in lymphocytes requires the recombination activating genes , rag 1 and rag 2 . ^^^ Here we report that rag 2 , the obligate partner for rag 1 function , is also expressed in OSNs and that its expression pattern mimics that of rag 1 . ^^^ The onset of rag 1 and rag 2 expression preceded that of known zebrafish ORs and the number of rag 1 positive OSNs corresponded with the number expressing the olfactory cyclic nucleotide gated cation channel , an OSN marker . ^^^ The expression of rag 1 and rag 2 in OSNs adds to the list of similarities between the olfactory and immune systems that includes monoallelic and mutually exclusive gene expression . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Identical mutations in RAG 1 or RAG 2 genes leading to defective 5 ( D ) J recombinase activity can cause either T B severe combined immune deficiency or Omenn syndrome . ^^^ Inherited mutations in either the recombination activating genes RAG 1 or RAG 2 , resulting in partial 5 ( D ) J recombinase activity , were shown to be responsible for OS . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 in 5 ( D ) J recombination and transposition . ^^^ RAG 1 and RAG 2 are the key components of the 5 ( D ) J recombinase machinery that catalyses the somatic gene rearrangements of antigen receptor genes during lymphocyte development . ^^^ The individual roles of RAG 1 and RAG 2 in 5 ( D ) J recombination and transposition reactions are discussed based on mutation analyses and structure predictions . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Another SCID , RAG 1 and RAG 2 recombinase deficiency , may produce a typical form with a characteristic T B NK + phenotype , Omenn ' s syndrome , or forms with an unexpected T B + NK + phenotype . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Identification of two topologically independent domains in RAG 1 and their role in macromolecular interactions relevant to 5 ( D ) J recombination . 5 ( D ) J recombination is instigated by the recombination activating proteins RAG 1 and RAG 2 , which catalyze site specific DNA cleavage at the border of the recombination signal sequence ( RSS ) . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
To examine the physiologic role of the second wave of RAG expression , we analyzed mice that can not reinduce RAG expression in CD 4 ( + ) CD 8 ( + ) T cells because the transgenic locus that directs RAG 1 and RAG 2 expression in these mice is missing a distal regulatory element essential for reinduction . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Mutations of the RAG 1 or RAG 2 protein that eliminate their recombination activity result in T B severe combined immunodeficiency ( SCID ) , whereas mutations retaining partial recombination activity lead to Omenn syndrome , a peculiar SCID characterized by increased host T cells and absence of circulating B cells . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Careful assessment of proliferation ( Ki 67 ) and apoptosis ( terminal dUTP nick end labeling ) indicators and of the occurrence of secondary immunoglobulin gene rearrangements ( RAG 1 and RAG 2 ) confirmed the parallelism . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Investigated was whether cotransfection of RAG 1 and RAG 2 genes in combination with lymphoid transcription factors can induce TCR gene rearrangements in nonlymphoid human cells . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Identification of basic residues in RAG 2 critical for DNA binding by the RAG 1 RAG2 complex . ^^^ In 5 ( D ) J recombination , the RAG 1 and RAG 2 proteins are the essential components of the complex that catalyzes DNA cleavage . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Somatic 5 ( D ) J recombination of the immune receptor genes is mediated by the recombination signal sequence ( RSS ) and the recombination activating genes RAG 1 and RAG 2 . ^^^ Notably , its affinity for the RSS decreased when RAG 1 and RAG 2 were induced . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
All 39 5 ( H ) elements ( with their adjacent heptamer / nonamer signal ) were tested for site specific cleavage with purified human core RAG 1 and RAG 2 , and HMG 1 proteins in a 12 / 23 coupled cleavage reaction . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
This complex , composed of a dimer of RAG 2 and at least a trimer of RAG 1 , remains inactive for double strand break formation until a second complementary signal is provided . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
We showed that Rag 1 ( C57BL / 6 background ) and Rag 2 ( BALB / c background ) knockout mice , which lack both T and B cells , chronically shed high levels of rotavirus Ag in stool samples following oral inoculation . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Early death and severe lymphopenia caused by ubiquitous expression of the Rag 1 and Rag 2 genes in mice . ^^^ The recombination activating proteins ( RAG 1 and RAG 2 ) are essential for 5 ( D ) J recombination of immunoglobulin chains . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 ( RAGs ) initiate 5 ( D ) J recombination by introducing breaks between two coding segments and flanking recombination signals ( RSs ) . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Expression of the recombination activating genes in extrafollicular lymphocytes but no apparent reinduction in germinal center reactions in human tonsils . 5 ( D ) J recombination in lymphocytes is mediated by 2 recombination activating genes , RAG 1 and RAG 2 , which are expressed during lymphocyte development in bone marrow and thymus . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The recombination activating gene 1 ( RAG 1 ) and RAG 2 are expressed specifically in immature lymphoid cells undergoing the recombination of antigen receptor genes . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Two lymphoid cell specific proteins , RAG 1 and RAG 2 , initiate 5 ( D ) J recombination by introducing DNA breaks at recombination signal sequences ( RSSs ) . ^^^ In contrast , 23 RSS complexes containing both RAG proteins and either HMG 1 or HMG 2 exhibited enhanced cleavage activity and displayed an altered distribution of cleavage products compared to 23 RSS complexes containing only RAG 1 and RAG 2 . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
PU . 1 expression can downregulate pre Talpha , Rag 1 , and Rag 2 in a dose dependent manner , and higher PU . 1 levels induce Mac 1 and Id 2 . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
In the other one , the DSB is made by the RAG 1 and RAG 2 proteins . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
These defects are attenuated in vivo , but bone marrow B cells display an unusual pattern of cell surface marker expression and show decreased transcript levels for TdT , Rag 1 , Rag 2 and lambda 5 . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
These cells had reduced expression of the recombinase activating genes , RAG 1 and RAG 2 . ^^^ Their receptor negative pre B cell progeny were relatively small , expressed RAG 1 and RAG 2 , and exhibited selective down regulation of VpreB and lambda 5 expression . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
A portion of these SCID patients bear a defect in either of the two recombination activating genes , Rag 1 or Rag 2 , while others have mutations in a newly identified gene , Artemis . ^^^ Omenn syndrome is an unusual severe immunodeficiency with T cells but no B cells , and peculiar features also due to a defect in Rag 1 or Rag 2 genes . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
To test the possibility that RAG 1 and RAG 2 differ in their roles in tumorigenesis , we studied Rag 1 ( / ) Atm ( / ) mice in parallel to our previous Rag 2 ( / ) Atm ( / ) study . ^^^ We found that thymic lymphomas occur at high frequency in Rag 1 ( / ) Atm ( / ) mice and resemble those that occur in Rag 2 ( / ) Atm ( / ) mice . ^^^ These results indicate that both RAG 1 and RAG 2 are necessary for tumorigenesis involving translocation in the Tcr alpha / delta locus but that Atm deficiency leads to tumors through a broader RAG independent predisposition to translocation , related to a generalized defect in dsDNA break repair . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Although both RAG 1 and RAG 2 are required for all steps of 5 ( D ) J recombination , little is known about the specific contribution of either protein to these steps . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
In genetic engineered B cells stably transfected with inducible expression vectors for the recombination activating genes RAG 1 , RAG 2 , or both , the avidity of KRC to DNA was markedly decreased when RAG 1 and RAG 2 were overexpressed . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Both transcription factors can interfere with expression of the Rag 1 and Rag 2 recombinases , while GATA 3 notably blocks PU . 1 and IL 7Ralpha expression , and PU . 1 reduces expression of HES 1 and c Myb . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The recombination activation genes , RAG 1 and RAG 2 , encode the critical components of the recombinase complex responsible for the generation of functional antigen receptor genes . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Recombination is initiated by the lymphoid specific RAG 1 and RAG 2 proteins , which cooperate to make double strand breaks at specific recognition sequences ( recombination signal sequences , RSSs ) . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
A population of peripheral B cells have been shown to express recombination activating gene products , RAG 1 and RAG 2 , which are considered to be involved in revising the B cell antigen receptor ( BCR ) in the periphery . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RESULTS : Analysis of bulk mRNA indicated that RAG 1 and RAG 2 mRNA were found routinely in peripheral B cells of patients with active SLE , but not in healthy subjects . ^^^ When assessed on a single cell basis , there was a 3 fold increase in the frequency of RAG 1 and RAG 2 expressing B cells in SLE patients compared with healthy subjects . ^^^ Notably , B cells expressing both RAG 1 and RAG 2 mRNA expressed only IgD mRNA , but not IgG mRNA . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The RAG 1 and RAG 2 proteins are the lymphoid specific factors essential for 5 ( D ) J recombination , the process that leads to the diversification of antigen receptors on B and T lymphocytes . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Recombination of gene segments at the immunoglobulin and T cell receptor loci requires that the RAG 1 and RAG 2 proteins bring together DNA signal sequences ( RSSs ) with 12 and 23 bp spacers into a synaptic complex and cleave the DNA . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Sequence conservation of RAG 1 and RAG 2 genes in hematologic malignancies . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The protein products of the recombination activating genes ( RAG 1 and RAG 2 ) initiate the formation of immunoglobulin ( Ig ) and T cell receptors , which are essential for B and T cell development , respectively . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Signaling initiated via the preBCR promotes cellular proliferation and RAG 1 and RAG 2 downregulation to interrupt the immunoglobulin 5 ( D ) J gene rearrangement process . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
In 5 ( D ) J joining of antigen receptor genes , two recombination signal sequences ( RSSs ) , 12 RSS and 23 RSS , are paired and complexed with the protein products of recombination activating genes RAG 1 and RAG 2 . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Our results showed that low levels of RAG 1 and RAG 2 mRNA were present in all T cell subpopulations except CD 3 ( + ) / CD4 ( ) T cells . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
By stroma replacement from MSS 62 cells to TBR 31 1 cells , DFC 28 cells were differentiated into very early B lymphoid stage characterized by c kit down regulation and induction of BP 1 and B lymphoid associated genes ( Pax 5 , CD 19 , TdT , Rag 1 , and Rag 2 ) . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
A RAG 1 / RAG 2 tetramer supports 12 / 23 regulated synapsis , cleavage , and transposition of 5 ( D ) J recombination signals . ^^^ Initiation of 5 ( D ) J recombination involves the synapsis and cleavage of a 12 / 23 pair of recombination signal sequences by RAG 1 and RAG 2 . ^^^ In the absence of HMG 1 , 1 found that two discrete RAG 1 / RAG 2 complexes are detected by mobility shift assay on all RSS substrates tested . ^^^ Both contain dimeric RAG 1 and either one or two RAG 2 subunits . ^^^ The addition of HMG 1 supershifts both complexes without altering the RAG protein stoichiometry . 1 find that 12 / 23 regulated recombination signal synapsis and cleavage are only supported in a protein DNA complex containing HMG 1 and a RAG 1 / RAG 2 tetramer . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Patients with mutations of either RAG 1 or RAG 2 genes suffer from severe combined immunodeficiency ( SCID ) characterized by the lack of T and B lymphocytes . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Previous in vitro studies defined the minimal regions of RAG 1 and RAG 2 essential for 5 ( D ) J recombination . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Inverse transposition by the RAG 1 and RAG 2 proteins : role reversal of donor and target DNA . ^^^ The lymphoid specific proteins RAG 1 and RAG 2 initiate 5 ( D ) J recombination by introducing DNA double strand breaks at the recombination signal sequences ( RSSs ) . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Finally , purified core RAG 1 and RAG 2 proteins ( together with HMG 2 ) also reproduce B12 / 23 restriction in a cell free system . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
A mutant truncated RAG 2 protein ( `` core ' ' RAG 2 ) lacking the C terminal 144 amino acids , together with core RAG 1 , is able to mediate the basic biochemical steps required for 5 ( D ) J recombination in vitro and in transfected cell lines . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
In common with other vertebrate species , the shark RAG 2 coding region lacks introns and is closely linked in opposite orientation to the RAG 1 gene . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
These DNA rearrangements involve cleavage by the RAG 1 and RAG 2 ( RAG1 / 2 ) recombinase enzymes at recombination signal sequences ( RSS ) . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 initiate 5 ( D ) J recombination , which is the assembly of immunoglobulin and T cell receptor genes . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
In analogy to human MLL , MLL ENL transformed cells not only coexpressed lymphocyte specific ( rag 1 , rag 2 , pax 5 , Tdt ) and monocyte specific genes ( lysozyme , c fms ) , but also showed rearrangements of the genomic immunoglobulin locus . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 initiate 5 ( D ) J recombination by introducing DNA double strand breaks between each selected gene segment and its bordering recombination signal sequence ( RSS ) in a two step mechanism in which the DNA is first nicked , followed by hairpin formation . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Therefore , CD 40 regulated expression of RAG 1 and RAG 2 in peripheral T cells may constitute a novel pathway for the generation of autoaggressive T cells . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 catalyze the initial DNA cleavage steps in 5 ( D ) J recombination . ^^^ Furthermore , core RAG 2 ( residues 1 387 ) formed complexes with multimeric RAG 1 species bound to a single RSS , providing additional support for the physiological relevance of higher order oligomeric states of RAG1 . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The RAG 1 and RAG 2 proteins perform critical DNA recognition and cleavage functions in 5 ( D ) J recombination , and also catalyze efficient DNA transposition in vitro . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Truncated forms of RAG 1 and RAG 2 are functional in vivo and have been used to study 5 ( D ) J cleavage , hybrid joint formation and transposition in vitro . ^^^ Although full length RAG 1 and RAG 2 proteins rarely form hybrid joints in vivo in the absence of non homologous end joining factors , we show that the full length proteins alone can catalyze this reaction in vitro . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Two lymphoid specific proteins , RAG 1 and RAG 2 , are required for the initiation of the 5 ( D ) J recombination in vitro . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
In vitro binding and cleavage assays using recombinant RAG 1 and RAG 2 proteins further validated the cRSS participation in this RAG mediated recombination process . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Thus , bone marrow TLPs are heterogenous with respect to TCRbeta rearrangement status , suggesting an active recombination machinery that is consistent with the expression of RAG 1 , RAG 2 , and TdT in this population . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Transcript expression of two Iglambda rearrangements and RAG 1 / RAG 2 in a mature human B cell producing IgMlambda islet cell autoantibody . ^^^ RAG 1 and RAG 2 transcripts occurred in EBV MB 91 but not in HY MB 91 , indicating that the former but not the latter might have been able to exhibit 5 ( D ) J recombinase activity . ^^^ Data show that a mature nonmalignant human B cell clone producing IgMlambda ICA can express RAG 1 / RAG 2 transcripts . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Expression of the recombinase proteins RAG 1 and RAG 2 is discordant : while RAG 1 is relatively long lived , RAG 2 is degraded periodically at the G ( 1 ) S transition . ^^^ RAG 1 or RAG 2 , expressed individually , is a nuclear protein . ^^^ RAG 1 rescued the localization of degradation defective , RAG 2 NLS mutants ; this required an intact RAG 1 NLS . ^^^ Recombination defects were correlated with a cell cycle dependent defect in the ability of RAG 1 to rescue localization of the RAG 2 mutants . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Recombination activating gene products , RAG 1 and RAG 2 , bind and cleave the cRSS to generate DNA deletion circles during the 5 ( H ) replacement process . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Although expression of the RAG 1 and RAG 2 genes is essential for lymphocyte development , the mechanisms responsible for the lymphoid and developmental stage specific regulation of these genes are poorly understood . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RT PCR and Western blotting were used to examine the expression of SNC 73 , recombination activating gene 1 ( RAG 1 ) , and RAG 2 . ^^^ RESULTS : The human epithelial cancer cell line ( SW 480 ) positively expressed SNC 73 , RAG 1 , and RAG 2 . ^^^ Both sequencing and Western blotting showed that the RAG 1 and RAG 2 expressed in SW 480 cells were identical to that expressed in pre B lymphocytes . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Here , we show that expression in Saccharomyces cerevisiae of murine RAG 1 and RAG 2 , the lymphoid specific components of the 5 ( D ) J recombinase , is sufficient to induce 5 ( D ) J cleavage and rejoining in this lower eukaryote . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The 5 ( D ) J recombination of TCRalpha and beta in early developing T cells is a highly modulated phenomenon initiated and completed by recombinase complex ( RAG 1 and RAG 2 ) , and regulated by other gene products such as interleukins . ^^^ To further evaluate the association of several other gene products with the evolution of TCRVbeta8 . 1 5 ( D ) J rearrangements in vivo , the mRNA expression levels of seven interleukins , three cytokines , receptors TCRVbeta8 . 1 and IL 2Rbeta , MHC I / MHC 2 , RAG 1 / RAG 2 and retroviral superantigen MMTV ( SW ) were measured by RT PCR during the fetal development of the thymus of three inbred mouse strains ( Balb c , C57B1 / 6 and CBA / J ) . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 are the lymphocyte specific components of the 5 ( D ) J recombinase . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Full length RAG 2 , and not full length RAG 1 , specifically suppresses RAG mediated transposition but not hybrid joint formation or disintegration . ^^^ RAG 1 and RAG 2 initiate 5 ( D ) J recombination by introducing DNA breaks at recombination signal sequences flanking a pair of antigen receptor gene segments . ^^^ From mammalian cells , full length RAG 1 is readily purified with core RAG 2 but not full length RAG 2 and vice versa . ^^^ Despite differences in DNA binding activity , recombinase containing either core or full length RAG 1 or RAG 2 possess comparable cleavage , rejoining , and end processing activity , as well as similar usage preferences for canonical versus cryptic recombination signals . ^^^ However , recombinase containing full length RAG 2 , but not full length RAG 1 , exhibits dramatically reduced transposition activity in vitro . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Using DNA microarrays and Northern blots to analyze unstimulated cells , we demonstrate that expression of a cluster of genes , including RAG 1 and RAG 2 , is repressed by constitutive signals requiring the adapter molecules LAT and SLP 76 . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Cell cycle dependent accumulation in vivo of transposition competent complexes between recombination signal ends and full length RAG proteins . 5 ( D ) J recombination is initiated by a specialized transposase consisting of RAG 1 and RAG 2 . ^^^ Because full length RAG proteins are insoluble under physiologic conditions , most previous analyses of RAG activity in vitro have used truncated core RAG 1 and RAG 2 fragments . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
We have tested the ability of this system to drive functional expression in vivo of the 5 ( D ) J recombination activating genes , RAG 1 and RAG 2 . ^^^ In induced transgenic mice , transgenic RAG 1 and RAG 2 mRNA is observed in thymus and spleen , and expression of both transgenes on the RAG 1 or RAG 2 knockout backgrounds allows partial , inducible , lymphocyte reconstitution . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Mutations in genes required for T cell development : IL7R , CD 45 , IL2RG , JAK 3 , RAG 1 , RAG 2 , ARTEMIS , and ADA and severe combined immunodeficiency : HuGE review . ^^^ Mutations in any of eight known genes : IL2RG , ARTEMIS , RAG 1 , RAG 2 , ADA , CD 45 , JAK 3 , and IL7R cause SCID . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
A spontaneous mutation in DNA PKcs of BALB / c mice results in SCID , as do experimentally induced mutations in RAG 1 and RAG 2 . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
It has been recently shown that mutations in both of the recombination activating genes RAG 1 and RAG 2 are involved in each of the two different types of severe combined immunodeficiency ( SCID ) syndromes : T B SCID and Omenn ' s syndrome ( OS ) . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Normal B cells did not express RAG 1 and RAG 2 spontaneously . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Here we review the prevalence of autoantibodies in the initial antibody repertoire , their regulation by receptor editing , and the role of the recombinase proteins ( RAG 1 and RAG 2 ) in this process . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
We determined DNA sequences of the nuclear encoded recombination activating genes ( Rag 1 and Rag 2 ) from all three major lungfish groups , the Australian Neoceratodis forsteri , the South American Lepidosiren paradoxa and the African lungfish Protopterus dolloi , and the Indonesian coelacanth Latimeria menadoensis . ^^^ Phylogenetic analyses of both the single gene and the concatenated data sets of RAG 1 and RAG 2 found that the lungfishes are the closest living relatives of the land vertebrates . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
We have identified a silencer and an antisilencing element that interact at a distance of 85 kilobases to regulate expression of the recombination activating genes Rag 1 and Rag 2 in thymocytes . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
During 5 ( D ) J recombination , the RAG 1 and RAG 2 proteins form a complex and initiate the process of rearrangement by cleaving between the coding and signal segments and generating hairpins at the coding ends . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Here we report that RAG 1 and RAG 2 proteins in the signal end ( SE ) complex cleave the 3 ' overhanging structure of the synthetic coding end ( CE ) DNA in two successive steps in vitro . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The acquisition of the capability of heterophilic antigen binding mode of interaction was apparently related to the introduction of recombination activating retroviral genes ( RAG 1 and RAG 2 ) into the genome of Gnathostomata ancestors . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The HARBI 1 proteins are conserved in humans , rats , mice , cows , pigs , chickens , frogs , and various bony fish , as well as other extremely important proteins , including RAG 1 and RAG 2 . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
It has been suggested that pre B cell receptor ( pre BCR ) signals are responsible for down regulation of the VDJH recombinase machinery ( Rag 1 , Rag 2 , and terminal deoxynucleotidyl transferase [ TdT ] ) , thereby preventing further rearrangement on the second HC allele . ^^^ Using a mouse model , we show that expression of an inducible muHC transgene in Rag 2 / pro B cells induces down regulation of the following : ( a ) TdT protein , ( b ) a transgenic green fluorescent protein reporter reflecting endogenous Rag 2 expression , and ( c ) Rag 1 primary transcripts . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
As is observed on naked DNA , in the presence of core RAG 1 , the full length RAG 2 protein proved to be more active than core RAG 2 on these polynucleosomal arrays , reinforcing the importance of the RAG 2 C terminal domain for efficient recombination . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Joining mutants of RAG 1 and RAG 2 that demonstrate impaired interactions with the coding end DNA . ^^^ In 5 ( D ) J joining of antigen receptor genes , two recombination signal sequences ( RSSs ) , 12 and 23 RSSs , form a complex with the protein products of recombination activating genes , RAG 1 and RAG 2 . ^^^ Joining mutants of RAG 1 and RAG 2 demonstrate impaired interactions with the coding region in both pre and postcleavage type complexes . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 1 and / or RAG 2 RNA was detected in PBMCs from 42 % of patients with IM but not from healthy control subjects . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 play a central role in 5 ( D ) J recombination , a process for antigen receptor gene assembly . ^^^ To investigate the role of the non core regions of RAGs in the end joining phase of antigen receptor rearrangement , we analyzed recombination products isolated from core RAG 1 and core RAG 2 knock in mice . ^^^ Signal joints ( SJs ) associated with 5 to D recombination of core RAG 1 knock in mice were normal , whereas those of core RAG 2 knock in mice were highly imprecise , containing large deletions and additions , and in some cases coding sequences . ^^^ In contrast , we found an elevated level of imprecise D to J associated SJs for both core RAG 1 and RAG 2 expressing mice . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Synapsis of recombination signal sequences located in cis and DNA underwinding in 5 ( D ) J recombination . 5 ( D ) J recombination requires binding and synapsis of a complementary ( 12 / 23 ) pair of recombination signal sequences ( RSSs ) by the RAG 1 and RAG 2 proteins , aided by a high mobility group protein , HMG 1 or HMG 2 . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
In particular , PBR expression induced several differentiation markers ( such as CD 1 , CD 6 ) , or key regulating elements ( e . g . , RAG 1 , RAG 2 , CD 99 , TCR ) . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
This site specific recombination reaction is initiated by a complex containing the RAG 1 and RAG 2 proteins and completed by general DNA repair factors . ^^^ RAG 1 and RAG 2 , like the adaptive immune system itself , are found exclusively in jawed vertebrates , and are thought to have entered the vertebrate genome by horizontal transmission as components of a transposable element . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Phylogenies based on over 2000 bp of two nuclear genes ( Rag 1 and Rag 2 ) identified reliably a clade of the Mantella betsileo and Mantella laevigata groups as sister lineage to the M . madagascariensis group , but did not support species within the latter group as monophyletic . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Intestinal samples from infants less than 6 mo old contained transcripts of T early alpha and TdT , and 15 of 19 infant samples contained mRNA for RAG 1 , some coexpressing RAG 2 . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
To further investigate the phylogenetic intrarelationships of discoglossids , nucleotide sequences of four nuclear protein coding genes ( CXCR 4 , RAG 1 , RAG 2 , and Rhodopsin ) with sequences available for the three discoglossid genera and Xenopus were retrieved from GenBank , and together with a concatenated nucleotide sequence data set containing all mt protein coding genes except ND 6 were subjected to separate and combined phylogenetic analyses . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
STI 571 treatment of leukemia patients induced expression of the Ig L chain associated transcription factors IRF 4 and SPIB , up regulation of RAG 1 and RAG 2 , Ckappa and Clambda germline transcription , and rearrangement of Ig kappa L chain ( IGK ) and Ig lambda L chain ( IGL ) genes . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RESULTS : TdT , RAG 1 , and RAG 2 were variably expressed . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
We will also discuss the consequences of integration in the genome by rag 1 and rag 2 genes ( recombination activating genes ) . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
In humans , most T ( ) B ( ) severe combined immunodeficiencies ( SCID ) have a defect in either the RAG 1 or RAG 2 gene , are not radiosensitive and do not show genome instability . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
In this study , we present evidence that activated mature CD 5 positive human tonsil B cells coexpress both RAG 1 and RAG 2 mRNA and protein , and display DNA cleavage resulting from their recombinase activity . ^^^ Furthermore , in vitro activation of CD 5 negative naive mature B cells by IgR and CD 40 cross linking induces expression of CD 5 on a subset of cells , and leads to the up regulation of RAG 1 and RAG 2 only in cells turned positive for CD 5 . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
OS patients carry leaky mutations of recombination activating genes ( RAG 1 or RAG 2 ) resulting in partial 5 ( D ) J recombination activity , whereas null mutations cause severe combined immunodeficiency with absence of mature T and B cells ( T B SCID ) . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The 5 ( D ) J recombination reaction in jawed vertebrates is catalyzed by the RAG 1 and RAG 2 proteins , which are believed to have emerged approximately 500 million years ago from transposon encoded proteins . ^^^ Yet no transposase sequence similar to RAG 1 or RAG 2 has been found . ^^^ We also suggest that the RAG 2 protein was not encoded by ancient Transib transposons but emerged in jawed vertebrates as a counterpart of RAG 1 necessary for the 5 ( D ) J recombination reaction . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
In addition , re expression of RAG 1 and RAG 2 in TCRbeta ( + ) cells is impaired , and the Valpha repertoire is altered . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The RAG 1 and RAG 2 proteins catalyze 5 ( D ) J recombination and are essential for generation of the diverse repertoire of antigen receptor genes and effective immune responses . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Carp rag 1 and rag 2 showed 90 and 89 % amino acid identity , respectively , to the corresponding zebrafish sequences . ^^^ From 1 wpf , rag 1 / rag 2 was expressed in kidney ( together with immunoglobulin heavy chain expression ) but not in spleen , while WCI12+ cells appeared 1 week later in both organs , suggesting B cell recombination in kidney but not in spleen . ^^^ Rag 1 expression exceeded rag 2 levels in thymus and in head and trunk kidney of juveniles , but this ratio was reversed in head and trunk kidney from approximately 16 wpf onwards . ^^^ Rag 1 / rag 2 expression was detected in thymi of animals over 1 year old , but in kidney only at low levels , indicating life long new formation of putative T cells but severely reduced formation of B cells in older fish . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The original rag allele found in W 50 was renamed rag 1 , while three novel alleles , rag 2 to rag 4 , were found in isolates lacking rag 1 . ^^^ In a laboratory collection of 168 isolates , 26 % carried rag 1 , 36 % carried rag 2 , 25 % carried rag 3 , and 14 % carried rag 4 ( including the type strain , ATCC 33277 ) . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Analysis of nuclear ( rag 1 , rag 2 , and rhodopsin genes ) and mitochondrial markers ( 12S and 16S ribosomal RNA genes ) provide evidence for an endemic clade of African genera of high morphological and ecological diversity thus far assigned to up to five different subfamilies : Afrana , Cacosternum , Natalobatrachus , Pyxicephalus , Strongylopus , and Tomopterna . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 initiate 5 ( D ) J recombination through synapsis and cleavage of a 12 / 23 pair of 5 ( D ) J recombination signal sequences ( RSS ) . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
In vertebrates , a diverse repertoire of antigen specific receptors , T cell receptors and immunoglobulins is generated by 5 ( D ) J recombination performed by the RAG 1 and RAG 2 protein complex . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
OBJECTIVE : The recombination activating enzymes RAG 1 and RAG 2 are essential to the process of 5 ( D ) J rearrangement in B and T cells and thus to the development of normal immune function . ^^^ Mutations in RAG 1 or RAG 2 can lead to a spectrum of disorders , ranging from typical ( B ) ( T ) severe combined immunodeficiency to Omenn ' s syndrome . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The DNA lesions can be introduced either by specific factors ( RAG 1 and RAG 2 in the case of 5 ( D ) J recombination and AID in the case of CSR and SHM ) or during the various phases of cellular proliferation and cellular activation . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Severe combined immunodeficiency ( SCID ) caused by mutations in RAG 1 or RAG 2 genes is characterized by a complete block in T and B cell development . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Transcripts of the RAG 1 and RAG 2 genes and earlier defined transcription factors , such as E2A , early B cell factor , E 2 2 , PAX 5 , and IRF 4 , were specifically up regulated at stages undergoing Ig gene rearrangements . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Amorphic mutations in the recombination activating genes RAG 1 and RAG 2 have been reported to cause T B SCID , whereas hypomorphic mutations led to the expansion of a few autoimmune T cell clones responsible for the Omenn syndrome phenotype . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Here we expand the molecular data to include DNA sequences , totaling 6192 base pairs ( bp ) , from nine nuclear protein coding genes ( C mos , RAG 1 , RAG 2 , R 35 , HOXA 13 , JUN , alpha enolase , amelogenin and MAFB ) for 19 taxa representing all major lineages . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 cleave DNA to generate blunt signal ends and hairpin coding ends at antigen receptor loci in lymphoid cells . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Moreover , deletion of either the RAG 2 or RAG 1 genes in B 6 mice was not associated with increased neuronal death at day 14 post axotomy , as we had previously found in B 6 mice with the severe combined immunodeficiency ( SCID ) mutation . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Transposition events into the target episome , accompanied by characteristic target site duplications , were detected at a low frequency using RAG 1 and either truncated `` core ' ' RAG 2 or full length RAG 2 . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The reaction , and its crucial mediators RAG 1 and RAG 2 , are essential for lymphocyte development and hence for adaptive immunity . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The Rag 1 and Rag 2 proteins are the key mediators of this process . ^^^ Here , we identify and characterize a closely linked pair of genes , SpRag1L and SpRag2L , from an invertebrate , the purple sea urchin ( Strongylocentrotus purpuratus ) with similarity in both sequence and genomic organization to the vertebrate Rag 1 and Rag 2 genes . ^^^ They are coexpressed during development and in adult tissues , and recombinant versions of the proteins form a stable complex with each other as well as with Rag 1 and Rag 2 proteins from several vertebrate species . ^^^ We thus conclude that SpRag1L and SpRag2L represent homologs of vertebrate Rag 1 and Rag 2 . ^^^ In combination with the apparent absence of 5 ( D ) J recombination in echinoderms , this finding strongly suggests that linked Rag 1 and Rag 2 like genes were already present and functioning in a different capacity in the common ancestor of living deuterostomes , and that their specific role in the adaptive immune system was acquired much later in an early jawed vertebrate . . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
DNA cleavage of a cryptic recombination signal sequence by RAG 1 and RAG 2 . ^^^ Recombination is initiated by cleavage of conserved recombination signal sequences ( RSS ) by RAG 1 and RAG 2 during lymphocyte development . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
Moreover , Pax 5 interacted with the recombination activating gene 1 ( RAG 1 ) RAG 2 complex to enhance RAG mediated 5 ( H ) recombination signal sequence cleavage and recombination of a 5 ( H ) gene substrate . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
RAG 1 and RAG 2 initiate 5 ( D ) J recombination by cleaving DNA at recombination signal sequences through sequential nicking and transesterification reactions to yield blunt signal ends and coding ends terminating in a DNA hairpin structure . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
The generation of developing B cells in the bone marrow is regulated by recombination activating genes RAG 1 and RAG 2 proteins . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
We correlate this arrest with up regulation of Bcl 2 , CD 2 , CD 5 , and CD 27 proteins and constitutive activation of NFAT but a severe impairment of Rag 1 , Rag 2 , and intracellular TCR beta as well as intracellular TCR gammadelta protein expression . ^^^ A correlation between the loss of NFAT activity and Rag 1 and Rag 2 expression is also found in myristoylated PKB induced CD4+ lymphoma cells . ^^^ Furthermore , ectopic expression of NFAT inhibits Rag 2 promoter activity in EL 4 cells , and in vivo binding of NFATc 1 to the Rag 1 and Rag 2 promoter and cis acting transcription regulatory elements is verified by chromatin immunoprecipitation analysis . ^^^ |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
NA |
|
Interacting proteins: P55895 and P15918 |
Pubmed |
SVM Score :0.0 |
NA |
|