Abstract:
Most organisms utilize meiosis, a specialized form of cell division, to produce reproductive cells such as sperm and eggs. Failure to maintain genomic integrity during meiosis can result in serious diseases, including infertility and cancer. The Structural Maintenance of Chromosomes 5/6 complex (SMC-5/6), its E3 SUMO ligase subunit NSE-2, and the BRCA1/BARD1 heterodimer are conserved protein complexes implicated in ensuring accurate meiotic DNA repair and are known to genetically interact. However, the specific mechanisms by which these proteins interact to preserve genome integrity is unknown. To determine the NSE-2 specific and NSE-2 independent meiotic functions of the SMC-5/6 complex in meiotic DSB repair, we utilized immunofluorescence imaging and a mortal germline phenotype assay to assess smc-5 and nse-2 C. elegans mutants. Our findings suggest a separation of function within the SMC-5/6 complex, which performs NSE-2 dependent functions promoting efficient meiotic DSB repair and NSE-2 independent functions in preservation of germline immortality. Finally, to define epistatic relationships between BRC-1/BRD-1, SMC-5/6, and NSE-2 in DNA repair, we assessed the germline sensitivity to exogenous DNA damage by scoring the brood viability of pairwise brc-1, smc-5, and nse-2 double mutants. These data reveal that exogenous DNA damage repair is differentially regulated within meiotic prophase I and implicate SMC-5/6 as a central regulator of both NSE-2 and BRC-1 dependent DSB repair. Taken together, our research defines fundamental genetic mechanisms and interactions preserving genomic integrity.