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bioRxiv · 10.1101/2024.04.12.589267

The chromatin-associated 53BP1 ortholog, HSR-9, regulates recombinational repair and X chromosome segregation in the Caenorhabditis elegans germ line

Li, Q.·Hariri, S.·Calidas, A.·Kaur, A.·Huey, E.·Engebrecht, J.
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Abstract

53BP1 plays a crucial role in regulating DNA damage repair pathway choice and checkpoint signaling in somatic cells; however, its role in meiosis has remained enigmatic. In this study, we demonstrate that the Caenorhabditis elegans ortholog of 53BP1, HSR-9, associates with chromatin in both proliferating and meiotic germ cells. Notably, HSR-9 is enriched on the X chromosome pair in pachytene oogenic germ cells. HSR-9 is also present at kinetochores during both mitotic and meiotic divisions but does not appear to be essential for monitoring microtubule-kinetochore attachments or tension. Using cytological markers of different steps in recombinational repair, we found that HSR-9 influences the processing of a subset of meiotic double strand breaks into COSA-1-marked crossovers. Additionally, HSR-9 plays a role in meiotic X chromosome segregation under conditions where X chromosomes fail to pair, synapse, and recombine. Together, these results highlight that chromatin-associated HSR-9 has both conserved and unique functions in the regulation of meiotic chromosome behavior. Article SummaryWhile 53BP1 is known for its crucial role in DNA damage signaling and repair in somatic cells, its role in meiosis is not well understood. Li, Hariri, et al., show that C. elegans 53BP1 not only functions in meiotic recombination and checkpoint signaling but also regulates the transmission of sex chromosomes when meiosis is perturbed. These results highlight the importance of 53BP1 in C. elegans meiosis and suggest that 53BP1 has both conserved and organism-specific functions.

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Li, Q., Hariri, S., Calidas, A., Kaur, A., Huey, E., Engebrecht, J.. 2024-04-15. The chromatin-associated 53BP1 ortholog, HSR-9, regulates recombinational repair and X chromosome segregation in the Caenorhabditis elegans germ line. https://doi.org/10.1101/2024.04.12.589267

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