Meiotic Double-Strand Break Processing and Crossover Patterning Are Regulated in a Sex-Specific Manner by BRCA1-BARD1...

Meiosis is regulated in a sex-specific manner to produce two distinct gametes, sperm and oocytes, for sexual reproduction. To determine how meiotic recombination is regulated in spermatogenesis, we analyzed the meiotic phenotypes of mutants in the tumor suppressor E3 ubiquitin ligase BRC-1-BRD-1 complex in Caenorhabditis elegans male meiosis. Unlike in mammals, this complex is not required for meiotic sex chromosome inactivation, the process whereby hemizygous sex chromosomes are transcriptionally silenced. Interestingly, brc-1 and brd-1 mutants show meiotic recombination phenotypes that are largely opposing to those previously reported for female meiosis. Fewer meiotic recombination intermediates marked by the recombinase RAD-51 were observed in brc-1 and brd-1 mutants, and the reduction in RAD-51 foci could be suppressed by mutation of nonhomologous-end-joining proteins. Analysis of GFP::RPA-1 revealed fewer foci in the brc-1brd-1 mutant and concentration of BRC-1-BRD-1 to sites of meiotic recombination was dependent on DNA end resection, suggesting that the complex regulates the processing of meiotic double-strand breaks to promote repair by homologous recombination. Further, BRC-1-BRD-1 is important to promote progeny viability when male meiosis is perturbed by mutations that block the pairing and synapsis of different chromosome pairs, although the complex is not required to stabilize the RAD-51 filament as in female meiosis under the same conditions. Analyses of crossover designation and formation revealed that BRC-1-BRD-1 inhibits supernumerary COs when meiosis is perturbed. Together, our findings suggest that BRC-1-BRD-1 regulates different aspects of meiotic recombination in male and female meiosis.