| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| Microinjection of cDNA encoding TFB 5 ( GTF2H5 , also called TTDA ) corrected the DNA repair defect of TTD A cells , and we identified three functional inactivating mutations in this gene in three unrelated families with TTD A . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| Using Southern blotting , we have analysed the ERCC 2 gene in DNA samples from 28 members of nine Italian families with individuals affected by XP D ( three patients ) or by TTD with photosensitivity due to the XP D defect ( eight patients ) . ^^^ No major modifications of the ERCC 2 gene were detected with two cDNA probes in either XP D or TTD patients indicating that the association between TTD and XP D is not likely to result from a large deletion or rearrangement involving this gene . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| Besides XP , mutations in XPD can cause another seemingly unrelated syndrome , trichothiodystrophy ( TTD ) , characterized by sulfur deficient brittle hair , ichthyosis , and physical and mental retardation . ^^^ Interestingly , the XPD variants containing TTD mutations fail to complement the lethality of the rad 3 null mutation , strongly suggesting that TTD mutations impair the ability of XPD protein to function normally in RNA polymerase 2 transcription . ^^^ From our studies , we conclude that XPD DNA helicase activity is not essential for transcription and infer that TTD mutations in XPD result in a defect in transcription . . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| We have now identified causative mutations in XPD in four TTD patients . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| Following the discovery that the human excision repair cross complementing rodent ultraviolet group 2 ( ERCC 2 ) gene is able to correct the ultraviolet sensitivity of XP D cell strains , the ERCC 2 cDNA from previous TTD patients was sequenced and shows frameshifts , deletions and point mutations in the ERCC 2 gene . ^^^ Molecular analysis of the defects in ERCC 2 in clinically distinct patients with XP , XP / Cockayne ' s syndrome , and TTD may provide insight into the molecular mechanisms of these genetically related but clinically distinct disorders . . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| In this work we describe the effect of ERCC 2 on the DNA repair deficient phenotype of XP D and on two repair defective TTD cell strains ( TTD1VI and TTD2VI ) assigned by complementation analysis to group D of XP . ^^^ ERCC 2 cDNA , cloned into a mammalian expression vector , was introduced into TTD and XP fibroblasts via DNA mediated transfection or microneedle injection . ^^^ These data show that a functional ERCC 2 gene is sufficient to reestablish a wild type DNA repair phenotype in TTD1VI and TTD2VI cells , confirming the genetic relationship between TTD and XP D . ^^^ Furthermore , our findings suggest that mutations at the ERCC 2 locus are responsible for causing a similar phenotype in TTD and XP D cells in response to UV irradiation , but produce quite different clinical symptoms . . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| Nucleotide sequence analysis of the ERCC 2 cDNA from three TTD cell strains ( TTD1V1 , TTD3VI , and TTD1RO ) revealed mutations within the region from amino acid 713 730 and within previously identified helicase functional domains . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| Although in both syndromes this defect is based on mutations in the same gene , XPD , only XP D , not TTD , individuals have an increased risk of skin cancer . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| Mutations in the XPD gene can result in three distinct clinical phenotypes , XP , trichothiodystrophy ( TTD ) , and XP with Cockayne syndrome . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| We have used the replicating shuttle vector pR 2 to determine the role of ultraviolet C ( UVC ) induced cyclobutane pyrimidine dimers ( CPDs ) and nondimer photoproducts in mutagenesis in human trichothiodystrophy ( TTD ) cells and in their repair proficient counterparts obtained after complementation with the wild type XPD / ERCC2 repair gene ( TTD + ERCC 2 cells ) . ^^^ The mutant frequency of the UV irradiated pR 2 plasmid treated by PR was similar after replication in TTD or in TTD + ERCC 2 cells . ^^^ In both cell lines , we observed that CPDs mostly led to GC AT transitions ; whereas only nondimer photoproducts were responsible for the induction of GC TA transversions in TTD and TTD + ERCC 2 cells . . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| The purpose of this study was to define the signals transmitted after UV C induced DNA damage , which activates p 53 accumulation in TTD / XP D fibroblasts , and compare this with XP D cell lines that carry different mutations in the same gene , XPD . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| To characterize nucleotide excision repair properties of cells from trichothiodystrophy ( TTD ) patients genetically related to the xeroderma pigmentosum ( XP ) group D , TTD skin fibroblasts from two unrelated patients ( TTD1VI and TTD2VI ) belonging to the TTD / XPD group were transformed with a plasmid containing SV 40 large T antigen coding sequences and some DNA repair properties , such as unscheduled DNA synthesis ( UDS ) , UV survival , in vitro repair synthesis of cell extracts and reactivation of UV irradiated reporter plasmid were studied . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| To determine whether expression of the XPD / ERCC2 repair gene in trichothiodystrophy ( TTD ) group D cells could restore mutagenesis characteristics of repair proficient cells , we compared the UV mutagenesis of normal cells , TTD group D cells , and TTD group D cells retrovirally transduced by the wild type XPD / ERCC2 gene ( TTD + ERCC 2 cells ) . ^^^ We first verified the expression of the XPD protein , correction of UV cell survival , and DNA repair ability of TTD + ERCC 2 cells . ^^^ The addition of the XPD / ERCC2 gene in TTD cells led to a significant but partial decrease of mutation frequency compared with the parental TTD cells . ^^^ In conclusion , the expression of the XPD / ERCC2 repair gene completely corrected UV hypersensitivity and almost all types of mutations of TTD group D cells , whereas hypermutagenesis was partially corrected . . ^^^ Types of mutations of TTD + ERCC 2 cells get closer to those observed in normal cells ( ie . , a reduction of multiple mutations ) . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| Here we report on two causative mutations of the XPD gene in XP61OS , a Japanese XP group D patient who has only mild skin symptoms of XP without CS , TTD , or other neurological complications . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| Patients with the nucleotide excision repair ( NER ) disorder xeroderma pigmentosum ( XP ) are highly predisposed to develop sunlight induced skin cancer , in remarkable contrast to photosensitive NER deficient trichothiodystrophy ( TTD ) patients carrying mutations in the same XPD gene . ^^^ To understand the relationship between deficient NER and tumor susceptibility , we used a mouse model for TTD that mimics an XPD point mutation of a TTD patient in the mouse germline . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| The DNA repair deficient genetic disorders xeroderma pigmentosum ( XP ) and trichothiodystrophy ( TTD ) can both result from mutations in the XPD gene , the sites of the mutations differing between the two disorders . ^^^ However , we also discovered that a subset of TTD cells , in which arg 112 in the NH 2 terminal region of the XPD protein is mutated to histidine , had an ICAM 1 response similar to that of XP D cells . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| The sun sensitive form of the severe neurodevelopmental , brittle hair disorder trichothiodystrophy ( TTD ) is caused by point mutations in the essential XPB and XPD helicase subunits of the dual functional DNA repair / basal transcription factor TFIIH . ^^^ Using a novel gene targeting strategy , we have mimicked the causative XPD point mutation of a TTD patient in the mouse . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| In most of the repair deficient TTD patients , the defect has been assigned to the XPD gene . ^^^ We have determined the mutations and the pattern of inheritance of the XPD alleles in the 11 cases identified in Italy so far , in which the hair abnormalities diagnostic for TTD are associated with different disease severity but similar cellular photosensitivity . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| Mutations in the XPD helicase gene result in XP and TTD phenotypes , preventing interaction between XPD and the p 44 subunit of TFIIH . ^^^ In most cases , xeroderma pigmentosum group D ( XP D ) and trichothiodystrophy ( TTD ) patients carry mutations in the carboxy terminal domain of the evolutionarily conserved helicase XPD , which is one of the subunits of the transcription / repair factor TFIIH ( refs 1 , 2 ) . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| In this paper we report that correction of the repair defect by retroviral mediated transduction of the wild type XPD gene in XP D and TTD / XP D untransformed primary fibroblasts leads to a normal p 53 response in these cells . ^^^ Thus , the complemented cells , like normal human fibroblasts , require higher UV doses ( 10 J / m2 ) for p 53 induction than the parental repair deficient XP D or TTD / XP D cells ( both mapping at the XPD locus ) , which accumulate p 53 protein at very low UV doses ( 2 . 5 and 5 J / m2 ) . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| Mutations in XPD helicase prevent its interaction and regulation by p 44 , another subunit of TFIIH , resulting in Xeroderma pigmentosum ( XP ) and trichothiodystrophy ( TTD ) phenotypes . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| TTD is a rare human genetic disease caused by mutations in XPB and XPD , two subunits of the transcription / repair factor TFIIH , and whose outstanding clinical characteristic is a lack of most human UHS proteins resulting in sulfur deficient brittle hair . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| Analysis of four XPD and four TTD / XPD fibroblast strains presenting different mutations on the XPD gene has shown that XPD cells are more sensitive to ultraviolet induced apoptosis than TTD / XPD cells , and this response seems to be modulated by the type and the location of the mutation on the XPD gene . ^^^ We have also found that cells from transcription coupled repair deficient XPA , XPD , TTD / XPD , and Cockayne ' s syndrome patients undergo apoptosis at lower ultraviolet doses than transcription coupled repair proficient cells ( normal human fibroblasts and XPC ) , indicating that blockage of RNA polymerase 2 at unrepaired lesions on the transcribed strand is the trigger . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| Mutations in the XPD helicase component of TFIIH can result in the diverse clinical features associated with xeroderma pigmentosum ( XP ) and trichothiodystrophy ( TTD ) . ^^^ Here we show that the specific mutations in XPD that cause TTD result in reduced expression of the beta globin genes in these individuals . ^^^ Eleven TTD patients with characterized mutations in the XPD gene have the haematological features of beta thalassaemia trait , and reduced levels of beta globin synthesis and beta globin mRNA . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| The repair deficient form of trichothiodystrophy ( TTD ) most often results from mutations in the genes XPB or XPD , encoding helicases of the transcription / repair factor TFIIH . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| Mutations in the XPD gene are associated with three complex clinical phenotypes , namely xeroderma pigmentosum ( XP ) , XP in combination with Cockayne syndrome ( XP CS ) , and trichothiodystrophy ( TTD ) . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| Different mutations in XPD give rise to three ultraviolet sensitive syndromes : the skin cancer prone disorder xeroderma pigmentosum ( XP ) , in which repair of ultraviolet damage is affected ; and the severe neurodevelopmental conditions Cockayne syndrome ( CS ) and trichothiodystrophy ( TTD ) . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| In UV sensitive TTD , the TFIIH transcription factor containing XPB and XPD helicase activities necessary for both transcription initiation and DNA repair is damaged . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| A recent study provides dramatic support for the so called transcription hypothesis of TTD . ( 1 ) Specifically , several patients have been shown to carry a mutation in the XPD gene , which encodes a thermolabile form of XPD protein , resulting in loss of hair during febrile episodes . . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| The XPD ( R658H ) TTD protein , like XPD ( T46I / R658H ) , is codominant when overexpressed in 5 H 1 cells and partially complements their UV sensitivity . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| We report a case of a combined immunodeficiency ( CID ) in a child affected by trichothiodystrophy ( TTD ) characterized by an altered response to ultraviolet ( UV ) light due to a defect in the XPD gene . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| Mutations in the XPD gene ( XPD ) can exhibit three distinct clinical phenotypes : XP , trichothiodystrophy ( TTD ) , or XP combined with Cockayne syndrome . ^^^ The findings are consistent with the hypothesis that the site of mutation of the XPD gene determines the clinical phenotype , XP or TTD . . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| Trichothiodystrophy ( TTD ) is a complex disorder caused by mutations in the XPD gene which affect both DNA repair and transcription . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| Trichothiodystrophy ( TTD ) is a rare hereditary multisystem disorder associated with defects in nucleotide excision repair ( NER ) as a consequence of mutations in XPD , XPB or TTDA , three genes that are all related to TFIIH , the multiprotein complex involved in NER and transcription . ^^^ We have also measured TFIIH levels in cells in which different mutations in the XPD gene are associated with clinical symptoms not of TTD but of the highly cancer prone disorder xeroderma pigmentosum ( XP ) . ^^^ We conclude that the severity of the clinical features in TTD patients and the clinical outcome of differentially mutated XPD proteins is likely to depend both on the effects that each mutation has on the stability of TFIIH and on the transcriptional activity of the residual TFIIH complexes . . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| Mutations in the XPD gene result in xeroderma pigmentosum ( XP ) and trichothiodystrophy ( TTD ) , the phenotypes of which are often intricate . ^^^ Moreover , when XPD mutations prevent interaction with the p 44 subunit of TFIIH , transactivation directed by certain nuclear receptors is inhibited , regardless of TTD versus XP phenotype , thus explaining the overlapping symptoms . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| XPC and TTD / XPD cell lines were complemented using retroviral transfer . ^^^ In both XPC and TTD / XPD complemented lines , CPD repair on the non transcribed strand is faster than that for the MRC5SV line . ^^^ Despite the slower global repair rate , in the complemented XPC and TTD / XPD cells , almost all of the CPDs at `` hotspots ' ' for mutation in the P 53 tumor database are repaired as rapidly as in normal human fibroblasts . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| On the other hand , confluent primary XPC and trichothiodystrophy ( TTD ) / XPD cell lines , related to xeroderma pigmentosum and trichothiodystrophy repair syndromes , had a reduced and delayed apoptosis when compared to non confluent cells . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| Most repair deficient TTD patients are mutated in the XPD gene , a subunit of the transcription factor TFIIH . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| A photosensitive form of trichothiodystrophy ( TTD ) results from mutations in the same XPD gene as the DNA repair deficient genetic disorder xeroderma pigmentosum group D ( XP D ) . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| Here , we provide strong support for this hypothesis by describing studies of mice with a mutation in XPD , a gene encoding a DNA helicase that functions in both repair and transcription and that is mutated in the human disorder trichothiodystrophy ( TTD ) . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| All three are genetically complex , with at least eight complementation groups for XP ( XP A to G and variant ) , five for CS ( CS A , CS B , XP B , XP D , and XP G ) , and three for TTD ( XP B , XP D , and TTD A ) . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| We report a 7 year old boy with TTD due to mutation in the XPD gene . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| Mutations in the XPD gene are found in XP , TTD and XP / CS patients , the latter exhibiting both XP and CS symptoms . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| Clinically relevant mutations in patients with trichothiodystrophy ( TTD ) and Fanconi anemia disrupt the Fe S clusters of XPD and FancJ and thereby abolish helicase activity . . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| Besides XPD and TTDA , the XPB gene product is also part of TFIIH . ^^^ One photosensitive TTD case constitutes a new repair deficient complementation group , TTD A . ^^^ Remarkably , both TTD A and XP D defects are associated with subunits of TFIIH , a basal transcription factor with a second function in DNA repair . ^^^ |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q6ZYL4 and P18074 |
Pubmed |
SVM Score :0.0 |
| NA |
|