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RPA与Rad52相互作用以促进减数分裂交叉和非交叉重组。

RPA interacts with Rad52 to promote meiotic crossover and noncrossover recombination.

作者信息

Joo Jeong H, Hong Soogil, Higashide Mika T, Choi Eui-Hwan, Yoon Seobin, Lee Min-Su, Kang Hyun Ah, Shinohara Akira, Kleckner Nancy, Kim Keun P

机构信息

Department of Life Sciences, Chung-Ang University, Seoul 06974, South Korea.

Institute for Protein Research, Graduate School of Science, Osaka University, Osaka 565-0871, Japan.

出版信息

Nucleic Acids Res. 2024 Apr 24;52(7):3794-3809. doi: 10.1093/nar/gkae083.

DOI:10.1093/nar/gkae083
PMID:38340339
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11040155/
Abstract

Meiotic recombination is initiated by programmed double-strand breaks (DSBs). Studies in Saccharomyces cerevisiae have shown that, following rapid resection to generate 3' single-stranded DNA (ssDNA) tails, one DSB end engages a homolog partner chromatid and is extended by DNA synthesis, whereas the other end remains associated with its sister. Then, after regulated differentiation into crossover- and noncrossover-fated types, the second DSB end participates in the reaction by strand annealing with the extended first end, along both pathways. This second-end capture is dependent on Rad52, presumably via its known capacity to anneal two ssDNAs. Here, using physical analysis of DNA recombination, we demonstrate that this process is dependent on direct interaction of Rad52 with the ssDNA binding protein, replication protein A (RPA). Furthermore, the absence of this Rad52-RPA joint activity results in a cytologically-prominent RPA spike, which emerges from the homolog axes at sites of crossovers during the pachytene stage of the meiotic prophase. Our findings suggest that this spike represents the DSB end of a broken chromatid caused by either the displaced leading DSB end or the second DSB end, which has been unable to engage with the partner homolog-associated ssDNA. These and other results imply a close correspondence between Rad52-RPA roles in meiotic recombination and mitotic DSB repair.

摘要

减数分裂重组由程序性双链断裂(DSB)启动。酿酒酵母中的研究表明,在快速切除以产生3'单链DNA(ssDNA)尾巴后,一个DSB末端与同源配对染色单体结合并通过DNA合成进行延伸,而另一端则与其姐妹染色单体保持关联。然后,在调控分化为交叉型和非交叉型命运类型后,第二个DSB末端通过与延伸的第一个末端进行链退火,沿着两条途径参与反应。这种第二个末端的捕获依赖于Rad52,大概是通过其已知的退火两条ssDNA的能力。在这里,我们通过对DNA重组的物理分析表明,这个过程依赖于Rad52与单链DNA结合蛋白复制蛋白A(RPA)的直接相互作用。此外,缺乏这种Rad52-RPA联合活性会导致在减数分裂前期粗线期交叉位点处从同源轴出现细胞学上显著的RPA峰。我们的研究结果表明,这个峰代表了由移位的领先DSB末端或第二个DSB末端导致的断裂染色单体的DSB末端,而第二个DSB末端无法与同源配对相关的ssDNA结合。这些以及其他结果暗示了Rad52-RPA在减数分裂重组和有丝分裂DSB修复中的作用之间存在密切对应关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3e/11040155/73d4789a2ade/gkae083fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3e/11040155/68b754ac3f13/gkae083figgra1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3e/11040155/b1e12a7a8927/gkae083fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3e/11040155/bd76dfd76b82/gkae083fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3e/11040155/56e89deabc74/gkae083fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3e/11040155/3a7191548013/gkae083fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3e/11040155/01cfb49dfde7/gkae083fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3e/11040155/caba05b85af1/gkae083fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3e/11040155/73d4789a2ade/gkae083fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3e/11040155/68b754ac3f13/gkae083figgra1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3e/11040155/b1e12a7a8927/gkae083fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3e/11040155/bd76dfd76b82/gkae083fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3e/11040155/56e89deabc74/gkae083fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3e/11040155/3a7191548013/gkae083fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3e/11040155/01cfb49dfde7/gkae083fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3e/11040155/caba05b85af1/gkae083fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3e/11040155/73d4789a2ade/gkae083fig7.jpg

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Nat Commun. 2023 Oct 5;14(1):6215. doi: 10.1038/s41467-023-41993-1.
2
Meiosis: Dances Between Homologs.减数分裂:同源染色体的舞蹈。
Annu Rev Genet. 2023 Nov 27;57:1-63. doi: 10.1146/annurev-genet-061323-044915. Epub 2023 Oct 3.
3
Meiotic prophase roles of Pds5 in recombination and chromosome condensation in budding yeast.减数分裂前期 Pds5 在芽殖酵母重组和染色体浓缩中的作用。
J Microbiol. 2022 Feb;60(2):177-186. doi: 10.1007/s12275-022-1635-9. Epub 2022 Feb 1.
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Repeated strand invasion and extensive branch migration are hallmarks of meiotic recombination.重复链入侵和广泛的分支迁移是减数分裂重组的标志。
Mol Cell. 2021 Oct 21;81(20):4258-4270.e4. doi: 10.1016/j.molcel.2021.08.003. Epub 2021 Aug 27.
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The synaptonemal complex central region modulates crossover pathways and feedback control of meiotic double-strand break formation.联会复合体中心区域调节交叉途径和减数分裂双链断裂形成的反馈控制。
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