Presenter(s): Alina Salagean
Faculty Mentor(s): Diana Libuda & Erik Toraason
Oral Session 3 M
Most organisms utilize meiosis, a specialized form of cell division, to produce haploid gametes such as sperm and eggs. Failure to maintain genomic integrity during meiosis can cause infertility and cancer. Using the model organism Caenorhabditis elegans, previous work has demonstrated that the conserved Structural Maintenance of Chromosomes 5/6 complex (SMC-5/6) is required for robust repair of double-strand DNA breaks (DSBs) in late meiotic prophase I. The specific mechanisms by which SMC-5/6 promotes DSB repair remain unknown. One subunit of the SMC- 5/6 complex, the E3 SUMO ligase NSE-2, has been implicated in DNA repair in multiple organisms. To identify the specific contributions of NSE-2 to meiotic DSB repair and fertility, we generated four nse-2 null mutants using CRISPR/Cas9 genome editing and assessed their phenotypes associated with genome integrity across generations. Utilizing these nse-2 mutants, we find that similarly to SMC-5, NSE-2 is required for a germ line-response to exogenous DNA damage. In contrast, unlike SMC-5, NSE-2 is not required for maintenance of fertility over generations. These data suggest NSE-2 is required for either a specific subset of functions of the SMC-5/6 complex or the efficient function of SMC-5/6. Our future experiments will utilize both genetic assays and immunofluorescence imaging techniques to distinguish between these hypotheses. Taken together, our research defines mechanisms preserving genomic integrity and fertility across generations.