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-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.
摘要:
53BP1在调节体细胞的DNA损伤修复途径选择和检查点信号传导中起着至关重要的作用;然而,它在减数分裂中的作用仍然是个谜。在这项研究中,我们证明53BP1,HSR-9的秀丽隐杆线虫直系同源物与增殖和减数分裂生殖细胞中的染色质相关。值得注意的是,HSR-9富集在粗线产卵生殖细胞的X染色体对上。HSR-9在有丝分裂和减数分裂分裂期间也存在于动静脉中,但对于监测微管-动静脉附着或张力似乎不是必需的。使用重组修复中不同步骤的细胞学标记,我们发现HSR-9会影响减数分裂双链断裂的子集加工成COSA-1标记的交叉。此外,在X染色体无法配对的条件下,HSR-9在减数分裂X染色体分离中起作用,突触,并重新组合。一起,这些结果强调了染色质相关的HSR-9在减数分裂染色体行为的调节中既保守又独特的功能。