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与染色质相关的53BP1直系同源物HSR-9在生殖系中调节重组修复和染色体分离。

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

作者信息

Li Qianyan, Hariri Sara, Calidas Aashna, Kaur Arshdeep, Huey Erica, Engebrecht JoAnne

机构信息

Department of Molecular and Cellular Biology, University of California Davis, Davis, California 95616.

Biochemistry, Molecular, Cellular and Developmental Biology Graduate Group, University of California Davis, Davis, California 95616.

出版信息

bioRxiv. 2024 Apr 15:2024.04.12.589267. doi: 10.1101/2024.04.12.589267.

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 ortholog of 53BP1, HSR-9, associates with chromatin in both proliferating and meiotic germ cells. Notably, HSR-9 is enriched on the 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 chromosome segregation under conditions where 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在调节体细胞中的DNA损伤修复途径选择和检查点信号传导中起着关键作用;然而,其在减数分裂中的作用仍然不明。在本研究中,我们证明53BP1的直系同源物HSR-9在增殖性和减数分裂性生殖细胞中均与染色质相关联。值得注意的是,HSR-9在粗线期卵子发生生殖细胞的染色体对上富集。在有丝分裂和减数分裂过程中,HSR-9也存在于动粒上,但似乎对于监测微管-动粒附着或张力并非必不可少。使用重组修复不同步骤的细胞学标记,我们发现HSR-9影响减数分裂双链断裂的一个子集加工成COSA-1标记的交叉。此外,在染色体未能配对、联会和重组的条件下,HSR-9在减数分裂染色体分离中发挥作用。总之,这些结果突出表明,与染色质相关的HSR-9在减数分裂染色体行为调控中具有保守和独特的功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0810/11042201/c9bb1d5c0dd2/nihpp-2024.04.12.589267v1-f0001.jpg

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