| Interacting proteins: Q14191 and P39748 |
Pubmed |
SVM Score :0.60879662 |
| The functional interaction between WRN and EXO 1 is mediated by a protein domain of WRN which interacts with flap endonuclease 1 ( FEN 1 ) . 0.60879662^^^ |
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| Interacting proteins: Q14191 and P39748 |
Pubmed |
SVM Score :1.4643051 |
| WRN was shown to facilitate FEN 1 binding to its preferred double flap substrate through its protein interaction with the FEN 1 C terminal binding site . 1.4643051^^^ The importance of the WRN / BLM physical interaction with the FEN 1 C terminal tail was confirmed by functional interaction studies with catalytically active purified recombinant FEN 1 deletion mutant proteins that lack either the WRN / BLM binding site or the PCNA interaction site . 0.74521607^^^ |
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| Interacting proteins: Q14191 and P39748 |
Pubmed |
SVM Score :0.0 |
| We report a novel interaction of the WRN gene product with the human 5 ' flap endonuclease / 5 ' 3 ' exonuclease ( FEN 1 ) , a DNA structure specific nuclease implicated in DNA replication , recombination and repair . ^^^ WS protein ( WRN ) dramatically stimulates the rate of FEN 1 cleavage of a 5 ' flap DNA substrate . ^^^ The WRN FEN 1 functional interaction is independent of WRN catalytic function and mediated by a 144 amino acid domain of WRN that shares homology with RecQ DNA helicases . ^^^ A physical interaction between WRN and FEN 1 is demonstrated by their co immunoprecipitation from HeLa cell lysate and affinity pull down experiments using a recombinant C terminal fragment of WRN . ^^^ The underlying defect of WS is discussed in light of the evidence for the interaction between WRN and FEN 1 . . ^^^ |
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| Interacting proteins: Q14191 and P39748 |
Pubmed |
SVM Score :0.0 |
| Biochemical characterization of the WRN FEN 1 functional interaction . ^^^ Recently we reported a novel interaction of the WRN gene product with human 5 ' flap endonuclease / 5 ' 3 ' exonuclease ( FEN 1 ) , a DNA structure specific nuclease implicated in pathways of DNA metabolism that are important for genomic stability . ^^^ To characterize the mechanism for WRN stimulation of FEN 1 cleavage , we have determined the effect of WRN on the kinetic parameters of the FEN 1 cleavage reaction . ^^^ WRN enhanced the efficiency of FEN 1 cleavage rather than DNA substrate binding . ^^^ WRN effectively stimulated FEN 1 cleavage on a flap DNA substrate with streptavidin bound to the terminal 3 ' nucleotide at the end of the upstream duplex , indicating that WRN does not require a free upstream end to stimulate FEN 1 cleavage of the 5 ' flap substrate . ^^^ |
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| Interacting proteins: Q14191 and P39748 |
Pubmed |
SVM Score :0.0 |
| WRN helicase and FEN 1 form a complex upon replication arrest and together process branchmigrating DNA structures associated with the replication fork . ^^^ Fluorescence resonance energy transfer ( FRET ) analyses show that WRN and Flap Endonuclease 1 ( FEN 1 ) form a complex in vivo that colocalizes in foci associated with arrested replication forks . ^^^ WRN effectively stimulates FEN 1 cleavage of branch migrating double flap structures that are the physiological substrates of FEN 1 during replication . ^^^ Biochemical analyses demonstrate that WRN helicase unwinds the chicken foot HJ intermediate associated with a regressed replication fork and stimulates FEN 1 to cleave the unwound product in a structure dependent manner . ^^^ These results provide evidence for an interaction between WRN and FEN 1 in vivo and suggest that these proteins function together to process DNA structures associated with the replication fork . . ^^^ |
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| Interacting proteins: Q14191 and P39748 |
Pubmed |
SVM Score :0.0 |
| To investigate the role of WRN in replication , we examined its ability to rescue cellular phenotypes of a yeast dna 2 mutant defective in a helicase endonuclease that participates with flap endonuclease 1 ( FEN 1 ) in Okazaki fragment processing . ^^^ WRN and yeast FEN 1 were reciprocally co immunoprecipitated from extracts of transformed dna 2 1 cells . ^^^ A physical interaction between yeast FEN 1 and WRN is demonstrated by yeast FEN 1 affinity pull down experiments using transformed dna 2 1 cells extracts and by ELISA assays with purified recombinant proteins . ^^^ Biochemical analyses demonstrate that the C terminal domain of WRN or BLM stimulates FEN 1 cleavage of its proposed physiological substrates during replication . ^^^ Collectively , the results suggest that the WRN FEN 1 interaction is biologically important in DNA metabolism and are consistent with a role of the conserved non catalytic domain of a human RecQ helicase in DNA replication intermediate processing . . ^^^ |
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| Interacting proteins: Q14191 and P39748 |
Pubmed |
SVM Score :0.0 |
| Moreover , the Lys 1016 mutation markedly reduced WRN helicase activity on fork , D loop , and Holliday junction substrates in addition to reducing significantly the ability of WRN to stimulate FEN 1 incision activities . ^^^ |
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| Interacting proteins: Q14191 and P39748 |
Pubmed |
SVM Score :0.0 |
| NA |
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