title: Biochemical Activities and Genetic Functions of the Drosophila melanogaster Fancm Helicase in DNA Repair.
abstract: Repair of DNA damage is essential to the preservation of genomic stability. During repair of double-strand breaks, several helicases function to promote accurate repair and prevent the formation of crossovers through homologous recombination. Among these helicases is the Fanconi anemia group M (FANCM) protein. FANCM is important in the response to various types of DNA damage and has been suggested to prevent mitotic crossovers during double-strand break repair. The helicase activity of FANCM is believed to be important in these functions, but no helicase activity has been detected in vitro We report here a genetic and biochemical study of Drosophila melanogaster Fancm. We show that purified Fancm is a 3' to 5' ATP-dependent helicase that can disassemble recombination intermediates, but only through limited lengths of duplex DNA. Using transgenic flies expressing full-length or truncated Fancm, each with either a wild-type or mutated helicase domain, we found that there are helicase-independent and C-terminal-independent functions in responding to DNA damage and in preventing mitotic crossovers.
authors.affiliation: Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina 27599.
authors.forename: Noelle-Erin
authors.initials: NE
authors.lastname: Romero
authors.affiliation: Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina 27599 Department of Biology, University of North Carolina, Chapel Hill, North Carolina 27599.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Matson
authors.affiliation: Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina 27599 Department of Biology, University of North Carolina, Chapel Hill, North Carolina 27599 Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, North Carolina 27599 sekelsky@unc.edu.
authors.forename: Jeff
authors.initials: J
authors.lastname: Sekelsky
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D003434:Crossing Over, Genetic; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage / Q000235:genetics; D004265:DNA Helicases / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D049750:Genome, Insect; D059765:Homologous Recombination / Q000235:genetics*; D008938:Mitosis / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; C000599214:FANCM protein, Drosophila; D004265:DNA Helicases
keywords: ATP activity; DNA helicase; biochemistry; crossing over; genetics; homologous recombination; synthesis-dependent strand annealing