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Genetics. 2004 Dec;168(4):2067-76.

End-joining repair of double-strand breaks in Drosophila melanogaster is largely DNA ligase IV independent.

Author information

1
Department of Biology, SPIRE Program, University of North Carolina, Chapel Hill, North Carolina 27599-3280, USA. mmcvey@email.unc.edu <mmcvey@email.unc.edu>

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.

PMID:
15611176
PMCID:
PMC1448732
DOI:
10.1534/genetics.104.033902
[Indexed for MEDLINE]
Free PMC Article

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