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减数分裂前期 Pds5 在芽殖酵母重组和染色体浓缩中的作用。

Meiotic prophase roles of Pds5 in recombination and chromosome condensation in budding yeast.

机构信息

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

出版信息

J Microbiol. 2022 Feb;60(2):177-186. doi: 10.1007/s12275-022-1635-9. Epub 2022 Feb 1.

DOI:10.1007/s12275-022-1635-9
PMID:35102525
Abstract

Genetic variation in eukaryotes is mediated during meiosis by the exchange of genetic material between homologous chromosomes to produce recombinant chromosomes. Cohesin is essential to promote proper chromosome segregation, chromosome morphogenesis, and recombination in meiotic cells. Cohesin consists of three main subunits-Smc1, Smc3, and the kleisin subunit Mcd1/Scc1 (Rec8 in meiosis)-and cohesin accessory factors. In Saccharomyces cerevisiae, the cohesin regulatory subunit Pds5 plays a role in homolog pairing, meiotic axis formation, and interhomolog recombination. In this study, we examine the prophase functions of Pds5 by performing physical analysis of recombination and three-dimensional high-resolution microscopy analysis to identify its roles in meiosis-specific recombination and chromosome morphogenesis. To investigate whether Pds5 plays a role in mitotic-like recombination, we inhibited Mek1 kinase activity, which resulted in switching to sister template bias by Rad51-dependent recombination. Reductions in double-strand breaks and crossover products and defective interhomolog recombination occurred in the absence of Pds5. Furthermore, recombination intermediates, including single-end invasion and double-Holliday junction, were reduced in the absence of Pds5 with Mek1 kinase inactivation compared to Mek1 kinase inactivation cells. Interestingly, the absence of Pds5 resulted in increasing numbers of chromosomes with hypercompaction of the chromosome axis. Thus, we suggest that Pds5 plays an essential role in recombination by suppressing the pairing of sister chromatids and abnormal compaction of the chromosome axis.

摘要

真核生物中的遗传变异是在减数分裂过程中通过同源染色体之间遗传物质的交换来介导的,从而产生重组染色体。黏合蛋白对于促进有丝分裂细胞中正确的染色体分离、染色体形态发生和重组是必不可少的。黏合蛋白由三个主要亚基-Smc1、Smc3 和 kleisin 亚基 Mcd1/Scc1(减数分裂中的 Rec8)-和黏合蛋白辅助因子组成。在酿酒酵母中,黏合蛋白调节亚基 Pds5 在同源配对、减数分裂轴形成和同源重组中发挥作用。在这项研究中,我们通过进行重组的物理分析和三维高分辨率显微镜分析来研究 Pds5 的前期功能,以确定其在减数分裂特异性重组和染色体形态发生中的作用。为了研究 Pds5 是否在有丝分裂样重组中发挥作用,我们抑制了 Mek1 激酶活性,这导致 Rad51 依赖性重组转向姐妹模板偏向。在没有 Pds5 的情况下,双链断裂和交叉产物减少,并且同源重组缺陷。此外,与 Mek1 激酶失活的细胞相比,在 Mek1 激酶失活的情况下,缺乏 Pds5 会减少包括单端入侵和双 Holliday 连接在内的重组中间体。有趣的是,缺乏 Pds5 会导致染色体轴超压缩的染色体数量增加。因此,我们认为 Pds5 通过抑制姐妹染色单体的配对和染色体轴的异常压缩在重组中发挥重要作用。

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Nucleic Acids Res. 2021 Jul 21;49(13):7537-7553. doi: 10.1093/nar/gkab566.
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Interplay between Pds5 and Rec8 in regulating chromosome axis length and crossover frequency.Pds5与Rec8在调节染色体轴长度和交叉频率中的相互作用。
Sci Adv. 2021 Mar 12;7(11). doi: 10.1126/sciadv.abe7920. Print 2021 Mar.
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A new role for the synaptonemal complex in the regulation of meiotic recombination.
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联会复合体在调控减数分裂重组中的新作用。
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