title: Formation of deletions during double-strand break repair in Drosophila DmBlm mutants occurs after strand invasion.
abstract: Bloom syndrome is a rare disorder associated with cancer predisposition and genomic instability and is caused by loss of the RecQ helicase BLM. The Drosophila ortholog of BLM (DmBlm) is required for accurate repair of DNA double-strand gaps by homologous recombination. Repair products from DmBlm mutants have shorter repair synthesis tract lengths compared to wild type and are frequently associated with deletions flanking the break site. To determine the mechanisms responsible for deletion formation in the absence of DmBlm, we characterized repair after excision of the P[w(a)] element in various genetic backgrounds. Flies lacking DmRad51 do not have an elevated deletion frequency. Moreover, loss of DmRad51 suppresses deletion formation in DmBlm mutants. These data support a model in which DmBlm acts downstream of strand invasion to unwind a D-loop intermediate to free the newly synthesized strand. In the absence of DmBlm, alternative pathways of D-loop disassembly result in short repair synthesis tracts or flanking deletions. This model explains how RecQ helicases can promote homologous recombination while preventing illegitimate recombination.
authors.affiliation: Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Mitch
authors.initials: M
authors.lastname: McVey
authors.forename: Jeannine R
authors.initials: JR
authors.lastname: Larocque
authors.forename: Melissa D
authors.initials: MD
authors.lastname: Adams
authors.forename: Jeff J
authors.initials: JJ
authors.lastname: Sekelsky
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019457:Chromosome Breakage; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins; D005260:Female; D017344:Genes, Insect; D008297:Male; D008957:Models, Genetic; D009154:Mutation; D017384:Sequence Deletion
chemical_list: D029721:Drosophila Proteins; D004247:DNA; D004265:DNA Helicases; C470639:blm protein, Drosophila