title: Drosophila ATR in double-strand break repair.
abstract: The ability of a cell to sense and respond to DNA damage is essential for genome stability. An important aspect of the response is arrest of the cell cycle, presumably to allow time for repair. Ataxia telangiectasia mutated (ATM) and ATR are essential for such cell-cycle control, but some observations suggest that they also play a direct role in DNA repair. The Drosophila ortholog of ATR, MEI-41, mediates the DNA damage-dependent G2-M checkpoint. We examined the role of MEI-41 in repair of double-strand breaks (DSBs) induced by P-element excision. We found that mei-41 mutants are defective in completing the later steps of homologous recombination repair, but have no defects in end-joining repair. We hypothesized that these repair defects are the result of loss of checkpoint control. To test this, we genetically reduced mitotic cyclin levels and also examined repair in grp (DmChk1) and lok (DmChk2) mutants. Our results suggest that a significant component of the repair defects is due to loss of MEI-41-dependent cell cycle regulation. However, this does not account for all of the defects we observed. We propose a novel role for MEI-41 in DSB repair, independent of the Chk1/Chk2-mediated checkpoint response.
authors.affiliation: Department of Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Jeannine R
authors.initials: JR
authors.lastname: LaRocque
authors.forename: Burnley
authors.initials: B
authors.lastname: Jaklevic
authors.forename: Tin Tin
authors.initials: TT
authors.lastname: Su
authors.forename: Jeff
authors.initials: J
authors.lastname: Sekelsky
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D004330:Drosophila / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D018816:Genes, cdc / Q000502:physiology; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D016601:RNA-Binding Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; C092281:PSI protein, Drosophila; D016601:RNA-Binding Proteins; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; D000071877:Checkpoint Kinase 1; C444435:Mei-41 protein, Drosophila; D017346:Protein Serine-Threonine Kinases; C000605877:grp protein, Drosophila; C112435:lok protein, Drosophila