Department of Molecular and Cellular Biology, University of California Davis, Davis, CA 95616, USA.
Biochemistry, Molecular, Cellular and Developmental Biology Graduate Group, University of California Davis, Davis, CA 95616, USA.
Genetics. 2024 Aug 7;227(4). doi: 10.1093/genetics/iyae102.
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-stranded 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.
53BP1 在调节体细胞中 DNA 损伤修复途径选择和检查点信号方面起着至关重要的作用;然而,其在减数分裂中的作用仍然是个谜。在这项研究中,我们证明了秀丽隐杆线虫中 53BP1 的同源物 HSR-9 与增殖和减数分裂生殖细胞中的染色质结合。值得注意的是,HSR-9 在减数分裂卵母细胞的粗线期在 X 染色体对上富集。HSR-9 在有丝分裂和减数分裂过程中也存在于动粒上,但似乎对监测微管-动粒连接或张力不是必需的。使用重组修复不同步骤的细胞学标记物,我们发现 HSR-9 影响将一部分减数分裂双链断裂加工成 COSA-1 标记的交叉。此外,在 X 染色体未能配对、联会和重组的情况下,HSR-9 在减数分裂 X 染色体分离中发挥作用。总之,这些结果强调了与染色质相关的 HSR-9 在调节减数分裂染色体行为方面具有保守和独特的功能。