title: Impaired resection of meiotic double-strand breaks channels repair to nonhomologous end joining in Caenorhabditis elegans.
abstract: Repair of double-strand DNA breaks (DSBs) by the homologous recombination (HR) pathway results in crossovers (COs) required for a successful first meiotic division. Mre11 is one member of the MRX/N (Mre11, Rad50, and Xrs2/Nbs1) complex required for meiotic DSB formation and for resection in Saccharomyces cerevisiae. In Caenorhabditis elegans, evidence for the MRX/N role in DSB resection is limited. We report the first separation-of-function allele, mre-11(iow1) in C. elegans, which is specifically defective in meiotic DSB resection but not in formation. The mre-11(iow1) mutants displayed chromosomal fragmentation and aggregation in late prophase I. Recombination intermediates and crossover formation was greatly reduced in mre-11(iow1) mutants. Irradiation-induced DSBs during meiosis failed to be repaired from early to middle prophase I in mre-11(iow1) mutants. In the absence of a functional HR, our data suggest that some DSBs in mre-11(iow1) mutants are repaired by the nonhomologous end joining (NHEJ) pathway, as removing NHEJ partially suppressed the meiotic defects shown by mre-11(iow1). In the absence of NHEJ and a functional MRX/N, meiotic DSBs are channeled to EXO-1-dependent HR repair. Overall, our analysis supports a role for MRE-11 in the resection of DSBs in middle meiotic prophase I and in blocking NHEJ.
authors.affiliation: Department of Biology, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Yin
authors.forename: Sarit
authors.initials: S
authors.lastname: Smolikove
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D017124:Conserved Sequence; D053903:DNA Breaks, Double-Stranded; D053837:DNA Cleavage; D059766:DNA End-Joining Repair; D005090:Exodeoxyribonucleases / Q000378:metabolism; D005804:Genes, Lethal; D049469:Meiotic Prophase I; D008969:Molecular Sequence Data; D017354:Point Mutation; D051135:Rad51 Recombinase / Q000378:metabolism; D011995:Recombination, Genetic; D059767:Recombinational DNA Repair
chemical_list: D029742:Caenorhabditis elegans Proteins; C423224:mre-11 protein, C elegans; D051135:Rad51 Recombinase; C495148:rad-51 protein, C elegans; D005090:Exodeoxyribonucleases; C028450:exodeoxyribonuclease I