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Impaired resection of meiotic double-strand breaks channels repair to nonhomologous end joining in Caenorhabditis elegans
Journal article   Peer reviewed

Impaired resection of meiotic double-strand breaks channels repair to nonhomologous end joining in Caenorhabditis elegans

Yizhi Yin and Sarit Smolikove
Molecular and cellular biology, Vol.33(14), pp.2732-2747
07/2013
DOI: 10.1128/MCB.00055-13
PMCID: PMC3700128
PMID: 23671188

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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.
Apoptosis Rad51 Recombinase - metabolism Amino Acid Sequence Recombinational DNA Repair Caenorhabditis elegans - genetics Caenorhabditis elegans Proteins - metabolism Molecular Sequence Data DNA Breaks, Double-Stranded Genes, Lethal Point Mutation Animals Caenorhabditis elegans - cytology Recombination, Genetic DNA End-Joining Repair Exodeoxyribonucleases - metabolism Meiotic Prophase I Conserved Sequence Caenorhabditis elegans Proteins - genetics DNA Cleavage

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