Impaired Resection of Meiotic Double-Strand Breaks Channels Repair to Nonhomologous End Joining in Caenorhabditis elegans

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 inSaccharomyces cerevisiae . InCaenorhabditis elegans , evidence for the MRX/N role in DSB resection is limited. We report the first separation-of-function allele,mre-11 (iow1 ) inC. elegans , which is specifically defective in meiotic DSB resection but not in formation. Themre-11 (iow1 ) mutants displayed chromosomal fragmentation and aggregation in late prophase I. Recombination intermediates and crossover formation was greatly reduced inmre-11 (iow1 ) mutants. Irradiation-induced DSBs during meiosis failed to be repaired from early to middle prophase I inmre-11 (iow1 ) mutants. In the absence of a functional HR, our data suggest that some DSBs inmre-11 (iow1 ) mutants are repaired by the nonhomologous end joining (NHEJ) pathway, as removing NHEJ partially suppressed the meiotic defects shown bymre-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.