Interacting proteins: Q14191 and P09874 |
Pubmed |
SVM Score :0.53113423 |
This review focuses on recent findings that demonstrate a functional interaction between WRN and two factors that bind to DNA breaks , Ku and poly ( ADP ribose ) polymerase 1 , and discuss how these interactions can influence fundamental cellular processes such as DNA repair , apoptosis and possibly regulate cell senescence and organismal aging . . 0.53113423^^^ |
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Interacting proteins: Q14191 and P09874 |
Pubmed |
SVM Score :0.70981678 |
Furthermore PARP 1 physically interacts with WRN , the protein deficient in Werner syndrome , a human progeroid disorder , and PARP 1 and WRN functionally cooperate in preventing carcinogenesis in vivo . 0.70981678^^^ |
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Interacting proteins: Q14191 and P09874 |
Pubmed |
SVM Score :0.0 |
METHODS : We analyzed 50 gastric carcinomas ( GCs ) for mutations in the BLM poly ( A ) tract aswell as in the coding microsatellites of the TGFbeta 1 RII , IGFIIR , hMSH 3 , hMSH 6 , BAX , WRN , RECQL and CBL genes . ^^^ |
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Interacting proteins: Q14191 and P09874 |
Pubmed |
SVM Score :0.0 |
In contrast , while the inhibition of poly ( ADP ribose ) polymerase ( PARP ) activity by 3 aminobenzamide increases the frequency of DNA deletion , mutant WRN mice are not significantly more sensitive to the inhibition of PARP activity than wild type animals . . ^^^ |
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Interacting proteins: Q14191 and P09874 |
Pubmed |
SVM Score :0.0 |
Genomic instability can be counteracted by a number of proteins including antioxidant enzymes , the WRN protein ( deficient in Werner syndrome ) , telomerase , poly ( ADP ribose ) polymerase 1 and a range other others , as well as by multi protein systems such as DNA mismatch repair , base excision repair and nucleotide excision repair . ^^^ |
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Interacting proteins: Q14191 and P09874 |
Pubmed |
SVM Score :0.0 |
Proteins with these dual roles occur in : ( 1 ) HRR ( BRCA 1 , ATM , ATR , WRN , BLM , Tip 60 and p 53 ) ; ( 2 ) NHEJ ( the catalytic subunit of DNA PK ) ; ( 3 ) NER ( XPB , XPD , p 53 and p 33 ( ING1b ) ) ; ( 4 ) BER ( Ref 1 / Ape , poly ( ADP ribose ) polymerase 1 ( PARP 1 ) and p 53 ) ; ( 5 ) MMR ( MSH 2 , MSH 6 , MLH 1 and PMS 2 ) . ^^^ |
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Interacting proteins: Q14191 and P09874 |
Pubmed |
SVM Score :0.0 |
To determine whether Wrn and PARP 1 enzymes act in concert during cell growth , mice with a mutation in the helicase domain of the Wrn gene ( Wrn ( Deltahel / Deltahel ) mice ) were crossed to PARP 1 null mice . ^^^ Both Wrn ( Deltahel / Deltahel ) and PARP 1 null / Wrn ( Deltahel / Deltahel ) cohorts developed more neoplasms than wild type animals . ^^^ The tumor spectrum was the same between PARP 1 null / Wrn ( Deltahel / Deltahel ) mice and Wrn mutants . ^^^ However , PARP 1 null / Wrn ( Deltahel / Deltahel ) mice developed neoplasms at a younger age . ^^^ Mouse embryonic fibroblasts derived from such PARP 1 null / Wrn ( Deltahel / Deltahel ) mice stop dividing abruptly unlike Wrn ( Deltahel / Deltahel ) or PARP 1 null cells . ^^^ |
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Interacting proteins: Q14191 and P09874 |
Pubmed |
SVM Score :0.0 |
In pursuit of a functional interaction between WRN and PARP 1 , we found that WS cells are deficient in the poly ( ADP ribosyl ) ation pathway after they are treated with the DNA damaging agents H2O2 and methyl methanesulfonate . ^^^ Overexpression of the PARP 1 binding domain of WRN strongly inhibits the poly ( ADP ribosyl ) ation activity in H2O2 treated control cell lines . ^^^ These results indicate that the WRN / PARP 1 complex plays a key role in the cellular response to oxidative stress and alkylating agents , suggesting a role for these proteins in the base excision DNA repair pathway . . ^^^ |
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Interacting proteins: Q14191 and P09874 |
Pubmed |
SVM Score :0.0 |
In the presence of DNA and NAD ( + ) , PARP 1 poly ( ADP ribosyl ) ates itself and Ku70 / 80 but not WRN , and gel shift assays showed that poly ( ADP ribosyl ) ation of Ku70 / 80 decreases the DNA binding affinity of this factor . ^^^ |
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Interacting proteins: Q14191 and P09874 |
Pubmed |
SVM Score :0.0 |
Recently we have identified poly ( ADP ribose ) polymerase 1 ( PARP 1 ) as a new WRN interacting protein . ^^^ We found that PARP 1 bound to the N terminus of WRN and to the C terminus containing the RecQ conserved ( RQC ) domain . ^^^ WRN bound to the N terminus of PARP 1 containing DNA binding and BRCA 1 C terminal ( BRCT ) domains . ^^^ We show that unmodified PARP 1 inhibited both WRN exonuclease and helicase activities , and to our knowledge is the only known WRN protein partner that inactivates both of the WRN ' s catalytic activities suggesting a biologically significant regulation . ^^^ Moreover , this dual inhibition seems to be specific for PARP 1 , as PARP 2 did not affect WRN helicase activity and only slightly inhibited WRN exonuclease activity . ^^^ |
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Interacting proteins: Q14191 and P09874 |
Pubmed |
SVM Score :0.0 |
To determine whether the mouse Werner syndrome homologue ( Wrn ) and the poly ( ADP ribose ) polymerase 1 ( PARP 1 ) enzymes act in concert to prevent specific chromosomal rearrangements , mice with a mutation in the helicase domain of the Wrn gene ( Wrn ( Deltahel / Deltahel ) mice ) were crossed to PARP 1 null mice . ^^^ Although there was no recurrent clonal chromosome aberration , PARP 1 null / Wrn ( Deltahel / Deltahel ) fibroblasts were distinguished by an increased frequency of chromatid breaks . ^^^ Interestingly , multiradial structures were the only type of DNA rearrangement that was significantly higher in such PARP 1 null / Wrn ( Deltahel / Deltahel ) cells . ^^^ These results indicate that Wrn and PARP 1 enzymes may be part of a protein complex involved in the processing of DNA breaks that can ultimately lead to multiradial structures when both enzymes are nonfunctional . ^^^ Finally , regions of chromosomes known to be fragile sites in the mouse genome are not more prone to DNA rearrangements in the absence of both PARP 1 and functional Wrn proteins . ^^^ |
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Interacting proteins: Q14191 and P09874 |
Pubmed |
SVM Score :0.0 |
The accumulation of WRN at double strand breaks was rapid , persisted for many hours , and occurred in the absence of several known interacting proteins including polymerase beta , poly ( ADP ribose ) polymerase 1 ( PARP 1 ) , Ku 80 , DNA dependent protein kinase ( DNA PKcs ) , NBS 1 and histone H2AX . ^^^ |
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Interacting proteins: Q14191 and P09874 |
Pubmed |
SVM Score :0.0 |
Interestingly , more than 58 % of misregulated genes identified in double mutant cells were not altered in cells with either the Wrn or PARP 1 mutation alone . ^^^ So , the impact on gene expression profile when both Wrn and PARP 1 are mutated was greater than a simple addition of individual mutant genotype . ^^^ |
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Interacting proteins: Q14191 and P09874 |
Pubmed |
SVM Score :0.0 |
NA |
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Interacting proteins: Q14191 and P09874 |
Pubmed |
SVM Score :0.0 |
NA |
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