title: End-joining repair of double-strand breaks in Drosophila melanogaster is largely DNA ligase IV independent.
abstract: Repair of DNA double-strand breaks can occur by either nonhomologous end joining or homologous recombination. Most nonhomologous end joining requires a specialized ligase, DNA ligase IV (Lig4). In Drosophila melanogaster, double-strand breaks created by excision of a P element are usually repaired by a homologous recombination pathway called synthesis-dependent strand annealing (SDSA). SDSA requires strand invasion mediated by DmRad51, the product of the spn-A gene. In spn-A mutants, repair proceeds through a nonconservative pathway involving the annealing of microhomologies found within the 17-nt overhangs produced by P excision. We report here that end joining of P-element breaks in the absence of DmRad51 does not require Drosophila LIG4. In wild-type flies, SDSA is sometimes incomplete, and repair is finished by an end-joining pathway that also appears to be independent of LIG4. Loss of LIG4 does not increase sensitivity to ionizing radiation in late-stage larvae, but lig4 spn-A double mutants do show heightened sensitivity relative to spn-A single mutants. Together, our results suggest that a LIG4-independent end-joining pathway is responsible for the majority of double-strand break repair in the absence of homologous recombination in flies.
authors.affiliation: Department of Biology, SPIRE Program, University of North Carolina, Chapel Hill, North Carolina 27599-3280, USA. mmcvey@email.unc.edu <mmcvey@email.unc.edu>
authors.forename: Mitch
authors.initials: M
authors.lastname: McVey
authors.forename: Dora
authors.initials: D
authors.lastname: Radut
authors.forename: Jeff J
authors.initials: JJ
authors.lastname: Sekelsky
mesh_terms: D000818:Animals; D004249:DNA Damage; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D004331:Drosophila melanogaster / Q000378:metabolism*; D009154:Mutation
chemical_list: D011088:DNA Ligases; D000072481:DNA Ligase ATP