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Werner syndrome protein interacts with human flap endonuclease 1 and stimulates its cleavage activity
Author(s) -
Brosh Robert M.,
von Kobbe Cayetano,
Sommers Joshua A.,
Karmakar Parimal,
Opresko Patricia L.,
Piotrowski Jason,
Dianova Irina,
Dianov Grigory L.,
Bohr Vilhelm A.
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.20.5791
Subject(s) - exonuclease , helicase , werner syndrome , nuclease , genome instability , biology , dna repair , microbiology and biotechnology , dna , endonuclease , immunoprecipitation , cleavage (geology) , dna replication , genetics , gene , dna damage , dna polymerase , rna , paleontology , fracture (geology)
Werner syndrome (WS) is a human premature aging disorder characterized by chromosomal instability. The cellular defects of WS presumably reflect compromised or aberrant function of a DNA metabolic pathway that under normal circumstances confers stability to the genome. 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.