title: Drosophila FANCM helicase prevents spontaneous mitotic crossovers generated by the MUS81 and SLX1 nucleases.
abstract: Several helicases function during repair of double-strand breaks and handling of blocked or stalled replication forks to promote pathways that prevent formation of crossovers. Among these are the Bloom syndrome helicase BLM and the Fanconi anemia group M (FANCM) helicase. To better understand functions of these helicases, we compared phenotypes of Drosophila melanogaster Blm and Fancm mutants. As previously reported for BLM, FANCM has roles in responding to several types of DNA damage in preventing mitotic and meiotic crossovers and in promoting the synthesis-dependent strand annealing pathway for repair of a double-strand gap. In most assays, the phenotype of Fancm mutants is less severe than that of Blm mutants, and the phenotype of Blm Fancm double mutants is more severe than either single mutant, indicating both overlapping and unique functions. It is thought that mitotic crossovers arise when structure-selective nucleases cleave DNA intermediates that would normally be unwound or disassembled by these helicases. When BLM is absent, three nucleases believed to function as Holliday junction resolvases--MUS81-MMS4, MUS312-SLX1, and GEN--become essential. In contrast, no single resolvase is essential in mutants lacking FANCM, although simultaneous loss of GEN and either of the others is lethal in Fancm mutants. Since Fancm mutants can tolerate loss of a single resolvase, we were able to show that spontaneous mitotic crossovers that occur when FANCM is missing are dependent on MUS312 and either MUS81 or SLX1.
authors.affiliation: Department of Biology, University of North Carolina, Chapel Hill, North Carolina 27599-7100.
authors.forename: H Kenny
authors.initials: HK
authors.lastname: Kuo
authors.affiliation: Department of Biology, University of North Carolina, Chapel Hill, North Carolina 27599-7100 Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, North Carolina 27599-7100.
authors.forename: Susan
authors.initials: S
authors.lastname: McMahan
authors.affiliation: Department of Biology, University of North Carolina, Chapel Hill, North Carolina 27599-7100.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Rota
authors.affiliation: Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina 27599-7100.
authors.forename: Kathryn P
authors.initials: KP
authors.lastname: Kohl
authors.affiliation: Department of Biology, University of North Carolina, Chapel Hill, North Carolina 27599-7100 Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, North Carolina 27599-7100 Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina 27599-7100 sekelsky@unc.edu.
authors.forename: Jeff
authors.initials: J
authors.lastname: Sekelsky
mesh_terms: D000818:Animals; D003434:Crossing Over, Genetic; D004249:DNA Damage; D004265:DNA Helicases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000201:enzymology / Q000235:genetics*; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism*; D049750:Genome, Insect; D008540:Meiosis / Q000235:genetics; D008938:Mitosis / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D045522:Recombinases / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D045522:Recombinases; D004706:Endodeoxyribonucleases; D004720:Endonucleases; C569843:SLX1 protein, Drosophila; C000599216:MUS81 protein, Drosophila; C000599214:FANCM protein, Drosophila; D004265:DNA Helicases
keywords: Fanconi anemia; Holliday junction resolvase; helicase; mitotic recombination