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BRCA1 通过激活染色体联会检查点来保护基因组完整性，以消除有缺陷的重组卵母细胞。

BRCA1 safeguards genome integrity by activating chromosome asynapsis checkpoint to eliminate recombination-defective oocytes.

机构信息

Key Laboratory of Reproductive Genetics (Ministry of Education) and Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.

Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou 310029, China.

出版信息

Proc Natl Acad Sci U S A. 2024 May 7;121(19):e2401386121. doi: 10.1073/pnas.2401386121. Epub 2024 May 2.

DOI:10.1073/pnas.2401386121
PMID:38696471
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11087798/
Abstract

In the meiotic prophase, programmed DNA double-strand breaks are repaired by meiotic recombination. Recombination-defective meiocytes are eliminated to preserve genome integrity in gametes. BRCA1 is a critical protein in somatic homologous recombination, but studies have suggested that BRCA1 is dispensable for meiotic recombination. Here we show that BRCA1 is essential for meiotic recombination. Interestingly, BRCA1 also has a function in eliminating recombination-defective oocytes. knockout (KO) rescues the survival of KO oocytes far more efficiently than removing CHK2, a vital component of the DNA damage checkpoint in oocytes. Mechanistically, BRCA1 activates chromosome asynapsis checkpoint by promoting ATR activity at unsynapsed chromosome axes in KO oocytes. Moreover, KO also rescues the survival of asynaptic KO oocytes. Collectively, our study not only unveils an unappreciated role of chromosome asynapsis in eliminating recombination-defective oocytes but also reveals the dual functions of BRCA1 in safeguarding oocyte genome integrity.

摘要

在减数分裂前期，程序性 DNA 双链断裂通过减数分裂重组修复。重组缺陷的减数分裂细胞被消除，以保持配子中的基因组完整性。BRCA1 是体细胞同源重组中的关键蛋白，但研究表明 BRCA1 对于减数分裂重组并非必需。在这里，我们表明 BRCA1 对于减数分裂重组是必需的。有趣的是，BRCA1 对于消除重组缺陷的卵母细胞也具有功能。BRCA1 敲除 (KO) 比去除卵母细胞中 DNA 损伤检查点的重要组成部分 CHK2 更有效地拯救 BRCA1 KO 卵母细胞的存活。从机制上讲，BRCA1 通过在 BRCA1 KO 卵母细胞中未联会的染色体轴上促进 ATR 活性来激活染色体联会检查点。此外，BRCA1 KO 也拯救了联会缺陷的 BRCA1 KO 卵母细胞的存活。总的来说，我们的研究不仅揭示了染色体联会在消除重组缺陷卵母细胞中的一个未被充分认识的作用，还揭示了 BRCA1 在保护卵母细胞基因组完整性方面的双重功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6637/11087798/4a8c8b7c3a99/pnas.2401386121fig08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6637/11087798/de878f051215/pnas.2401386121fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6637/11087798/cc575b3570f8/pnas.2401386121fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6637/11087798/5a99701be405/pnas.2401386121fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6637/11087798/4dab3acebf75/pnas.2401386121fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6637/11087798/9488c3bb278f/pnas.2401386121fig05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6637/11087798/bd18da12c9d4/pnas.2401386121fig06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6637/11087798/c3a11014abf0/pnas.2401386121fig07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6637/11087798/4a8c8b7c3a99/pnas.2401386121fig08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6637/11087798/de878f051215/pnas.2401386121fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6637/11087798/cc575b3570f8/pnas.2401386121fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6637/11087798/5a99701be405/pnas.2401386121fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6637/11087798/4dab3acebf75/pnas.2401386121fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6637/11087798/9488c3bb278f/pnas.2401386121fig05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6637/11087798/bd18da12c9d4/pnas.2401386121fig06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6637/11087798/c3a11014abf0/pnas.2401386121fig07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6637/11087798/4a8c8b7c3a99/pnas.2401386121fig08.jpg

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4
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