PT  - JOURNAL ARTICLE
AU  - Erik Toraason
AU  - Alina Salagean
AU  - David E. Almanzar
AU  - Ofer Rog
AU  - Diana E. Libuda
TI  - BRCA1/BRC-1 and SMC-5/6 regulate DNA repair pathway engagement during <em>C. elegans</em> meiosis
AID  - 10.1101/2022.06.12.495837
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.06.12.495837
4099  - http://biorxiv.org/content/early/2022/06/14/2022.06.12.495837.short
4100  - http://biorxiv.org/content/early/2022/06/14/2022.06.12.495837.full
AB  - The preservation of genome integrity during sperm and egg development is vital for reproductive success. During meiosis, the tumor suppressor BRCA1/BRC-1 and structural maintenance of chromosomes 5/6 (SMC-5/6) complex genetically interact to promote high fidelity DNA double strand break (DSB) repair, but the specific DSB repair outcomes these proteins regulate remain unknown. Here we show that BRCA1/BRC-1 and the SMC-5/6 complex limit intersister crossover recombination as well as error-prone repair pathways during meiotic prophase I. Using genetic and cytological methods to monitor repair of DSBs with different repair partners in Caenorhabditis elegans, we demonstrate that both BRC-1 and SMC-5/6 repress intersister crossover recombination events, with meiotic cells becoming more dependent upon these proteins to repair DSBs in late meiotic prophase I. Sequencing of conversion tracts from homolog-independent DSB repair events indicates that BRC-1 regulates intersister/intrachromatid noncrossover conversion tract length. Moreover, we find that BRC-1 also specifically inhibits error prone repair of DSBs induced at mid-pachytene. Finally, we reveal that functional BRC-1 enhances DSB repair defects in smc-5 mutants by repressing theta-mediated end joining (TMEJ). Taken together, our study illuminates the coordinate interplay of BRC-1 and SMC-5/6 to regulate DSB repair outcomes in the germline.Competing Interest StatementThe authors have declared no competing interest.