title: Human Fanconi anemia complementation group a protein stimulates the 5' flap endonuclease activity of FEN1.
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.
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Liangyue
authors.initials: L
authors.lastname: Qian
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Yuan
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Paola
authors.initials: P
authors.lastname: Rodriguez-Tello
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Suyog
authors.initials: S
authors.lastname: Padgaonkar
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D004789:Enzyme Activation; D052217:Fanconi Anemia Complementation Group A Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D045585:Flap Endonucleases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D009154:Mutation; D054730:Protein Interaction Domains and Motifs
chemical_list: D052217:Fanconi Anemia Complementation Group A Protein; D045585:Flap Endonucleases