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Werner syndrome protein interacts with human flap endonuclease 1 and stimulates its cleavage activity.

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.

Pubmed ID: 11598021


  • Brosh RM
  • von Kobbe C
  • Sommers JA
  • Karmakar P
  • Opresko PL
  • Piotrowski J
  • Dianova I
  • Dianov GL
  • Bohr VA


The EMBO journal

Publication Data

October 15, 2001

Associated Grants


Mesh Terms

  • Adenosine Triphosphatases
  • Catalysis
  • DNA
  • DNA Helicases
  • DNA-Binding Proteins
  • Endodeoxyribonucleases
  • Enzyme Activation
  • Exodeoxyribonucleases
  • Exonucleases
  • Flap Endonucleases
  • HeLa Cells
  • Humans
  • Macromolecular Substances
  • Peptide Fragments
  • Proliferating Cell Nuclear Antigen
  • Protein Structure, Tertiary
  • RecQ Helicases
  • Recombinant Fusion Proteins
  • Replication Protein A
  • Werner Syndrome