PDF(Pubmed)
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. Brca1 knockout (KO) rescues the survival of Dmc1 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 Dmc1 KO oocytes. Moreover, Brca1 KO also rescues the survival of asynaptic Spo11 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。消除重组缺陷细胞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对于减数分裂重组是可有可无的。在这里，我们表明BRCA1对于减数分裂重组是必不可少的。有趣的是,BRCA1还具有消除重组缺陷型卵母细胞的功能。Brca1敲除（KO）比去除CHK2更有效地挽救Dmc1KO卵母细胞的存活，CHK2是卵母细胞中DNA损伤检查点的重要组成部分。机械上,BRCA1通过促进Dmc1KO卵母细胞未突触染色体轴处的ATR活性来激活染色体突触检查点。此外，Brca1KO还挽救了突触Spo11KO卵母细胞的存活。总的来说，我们的研究不仅揭示了染色体脱节在消除重组缺陷卵母细胞中的未被重视的作用,而且揭示了BRCA1在保护卵母细胞基因组完整性方面的双重功能.
