Human fanconi anemia complementation group a protein stimulates the 5′ flap endonuclease activity of FEN1

Liangyue Qian, Fenghua Yuan, Paola Rodriguez-Tello, Suyog Padgaonkar, Yanbin Zhang

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

In eukaryotic cells, Flap endonuclease 1 (FEN1) is a major structure-specific endonuclease that processes 5′ flapped structures during maturation of lagging strand DNA synthesis, long patch base excision repair, and rescue of stalled replication forks. Here we report that fanconi anemia complementation group A protein (FANCA), a protein that recognizes 5′ flap structures and is involved in DNA repair and maintenance of replication forks, constantly stimulates FEN1-mediated incision of both DNA and RNA flaps. Kinetic analyses indicate that FANCA stimulates FEN1 by increasing the turnover rate of FEN1 and altering its substrate affinity. More importantly, six pathogenic FANCA mutants are significantly less efficient than the wild-type at stimulating FEN1 endonuclease activity, implicating that regulation of FEN1 by FANCA contributes to the maintenance of genomic stability.

Original languageEnglish (US)
Article numbere82666
JournalPloS one
Volume8
Issue number12
DOIs
StatePublished - Dec 4 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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