SMC-5/6 Facilitates Efficient DSB Repair During Meiosis in C. elegans

Presenter(s): Cordell Clark − Biology

Faculty Mentor(s): Diana Libuda, Erik Toraason

Poster 73

Oral Session 3M

Research Area: Biological Science

Funding: OURS Program Summer 2017, Dr. Diana Libuda’s laboratory is funded in part by an NICHD grant

Sexually reproducing organisms depend upon meiosis to form haploid sex cells necessary for reproduction. Despite the inherent risks of DNA damage to genome integrity, meiotic cells intentionally induce double strand DNA breaks (DSBs) throughout the genome. A specific and limited number of DSBs must be repaired as crossovers with the homologous chromosome to promote proper chromosome segregation. DSBs are induced in excess of the permitted number of crossovers. DSBs not repaired as crossovers must be repaired to maintain genomic integrity. In the Libuda lab, we have designed an assay to determine the repair outcome of a single induced DSB. We have demonstrated that in addition to the homologous chromosome, the sister chromatid is used as a repair template during DSB repair in C. elegans meiosis. My research aims to uncover the mechanisms that facilitate intersister repair, which are currently unknown. Experiments in multiple species have demonstrated that SUMOylation is required for crossover formation. Our preliminary immunofluorescence experiments in SUMO deficient mutants reveal SUMOylation is required for DSB repair in C. elegans oocytes. Prior research has hypothesized that the SMC5/6 complex, which contains a SUMO ligase subunit (NSE-2), facilitates intersister recombination. Using our intersister repair assay, I have demonstrated that the SMC5/6 complex is required for efficient intersister repair and intersister crossovers. My ongoing experiments are directly testing whether the SMC5/6 complex promotes intersister recombination via the NSE-2 SUMO ligase subunit. Overall, our studies are defining the mechanisms that facilitate intersister recombination to ensure genome integrity during sperm and egg development.

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