Structure of the DNA Repair and Replication Endonuclease and Exonuclease FEN-1

  • Hosfield D
  • Mol C
  • Shen B
  • et al.
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Flap endonuclease (FEN-1) removes 5′ overhanging flaps in DNA repair and processes the 5′ ends of Okazaki fragments in lagging strand DNA synthesis. The crystal structure of Pyrococcus furiosus FEN-1, active-site metal ions, and mutational information indicate interactions for the single- and double-stranded portions of the flap DNA substrate and identify an unusual DNA-binding motif. The enzyme’s active-site structure suggests that DNA binding induces FEN-1 to clamp onto the cleavage junction to form the productive complex. The conserved FEN-1 C terminus binds proliferating cell nuclear antigen (PCNA) and positions FEN-1 to act primarily as an exonuclease in DNA replication, in contrast to its endonuclease activity in DNA repair. FEN-1 mutations altering PCNA binding should reduce activity during replication, likely causing DNA repeat expansions as seen in some cancers and genetic diseases.




Hosfield, D. J., Mol, C. D., Shen, B., & Tainer, J. A. (1998). Structure of the DNA Repair and Replication Endonuclease and Exonuclease FEN-1. Cell, 95(1), 135–146.

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