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.

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Correction for Yin and Smolikove, Impaired Resection of Meiotic Double-Strand Breaks Channels Repair to Nonhomologous End Joining in Caenorhabditis elegans

SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at http://dx.doi.org/10.1128/MCB.00055-13.

ACKNOWLEDGMENTS

Some strains and clones were kindly provided by the Caenorhabditis Genetics Center, which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440), and the C. elegans Reverse Genetics Core Facility at UBC, which is part of the International C. elegans Gene Knockout Consortium. We thank S. Boulton for the MRE-11 antibody, M. Hengartner for the RPA-1::YFP strain, and R. Chan for sharing protocols. We thank the Radiation and Free Radical Research Core Facility in the Carver College of Medicine for the irradiation service. We are grateful to R. E. Malone, J. A. Weiner, and members of the Smolikove lab for critical reading of the manuscript.

This work was supported by National Science Foundation grant MCB-1121150 (to S.S.) and UI startup funds (to S.S.).