Abstract
Breast cancer susceptibility gene 1(BRCA1) and binding partner BRCA1-associated RING domain protein 1 (BARD1) form an essential E3 ubiquitin ligase important for DNA damage repair and homologous recombination. In Caenorhabditis elegans BRCA1/BRC-1 and BARD1/BRD-1 orthologs are not essential, but function in DNA damage repair and homologous recombination, as well as in meiosis. In proliferating germ cells and in early meiotic prophase, BRC-1 and BRD-1 are nucleoplasmic, with enrichment at foci that partially overlap with the recombinase RAD-51. In mid-pachytene, BRC-1 and BRD-1 are observed on tracks, before concentrating to the short arms of bivalents, co-localizing with a central region component of the synaptonemal complex. We found that BRD-1 is essential for BRC-1 to associate with chromatin and the synaptonemal complex, but BRC-1 is not required for BRD-1 localization; the complex fails to properly localize in the absence of either meiotic recombination or chromosome synapsis. Inactivation of BRC-1/BRD-1 enhances the embryonic lethality of mutants that perturb chromosome synapsis and crossover recombination, suggesting that BRC-1/BRD-1 plays an important role in monitoring recombination in the context of the synaptonemal complex. We discovered that BRC-1/BRD-1 stabilizes the RAD51 filament when the formation of a crossover-intermediate is disrupted. Further, in the absence of BRC-1/BRD-1 crossover distribution is altered, and under meiotic dysfunction, crossover numbers are perturbed. Together, our studies indicate that BRC-1/BRD-1 localizes to the synaptonemal complex where it serves a checkpoint function to monitor and modulate meiotic recombination.
