Liu Chao, Xu Wei, Wang Liying, Yang Zhuo, Li Kuan, Hu Jun, Chen Yinghong, Zhang Ruidan, Xiao Sai, Liu Wenwen, Wei Huafang, Chen Jia-Yu, Sun Qianwen, Li Wei
Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China.
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Stem Cell and Regenerative Medicine Innovation Institute, Chinese Academy of Sciences, Beijing, 100101, China.
Cell Biosci. 2023 May 11;13(1):82. doi: 10.1186/s13578-023-01026-2.
Meiotic recombination is initiated by Spo11-dependent programmed DNA double-strand breaks (DSBs) that are preferentially concentrated within genomic regions called hotspots; however, the factor(s) that specify the positions of meiotic DSB hotspots remain unclear.
Here, we examined the frequency and distribution of R-loops, a type of functional chromatin structure comprising single-stranded DNA and a DNA:RNA hybrid, during budding yeast meiosis and found that the R-loops were changed dramatically throughout meiosis. We detected the formation of multiple de novo R-loops in the pachytene stage and found that these R-loops were associated with meiotic recombination during yeast meiosis. We show that transcription-replication head-on collisions could promote R-loop formation during meiotic DNA replication, and these R-loops are associated with Spo11. Furthermore, meiotic recombination hotspots can be eliminated by reversing the direction of transcription or replication, and reversing both of these directions can reconstitute the hotspots.
Our study reveals that R-loops may play dual roles in meiotic recombination. In addition to participation in meiotic DSB processing, some meiotic DSB hotspots may be originated from the transcription-replication head-on collisions during meiotic DNA replication.
减数分裂重组由依赖Spo11的程序性DNA双链断裂（DSB）引发，这些断裂优先集中在称为热点的基因组区域内；然而，决定减数分裂DSB热点位置的因素仍不清楚。
在这里，我们研究了R环（一种由单链DNA和DNA:RNA杂交体组成的功能性染色质结构）在芽殖酵母减数分裂过程中的频率和分布，发现R环在整个减数分裂过程中发生了显著变化。我们在粗线期检测到多个新生R环的形成，并发现这些R环与酵母减数分裂过程中的减数分裂重组相关。我们表明，转录-复制正面碰撞可在减数分裂DNA复制过程中促进R环形成，并且这些R环与Spo11相关。此外，通过逆转转录或复制方向可以消除减数分裂重组热点，而同时逆转这两个方向可以重新构建热点。
我们的研究表明，R环可能在减数分裂重组中发挥双重作用。除了参与减数分裂DSB加工外，一些减数分裂DSB热点可能源于减数分裂DNA复制过程中的转录-复制正面碰撞。
