The synaptonemal complex central region modulates crossover pathways and feedback control of meiotic double-strand break formation.

The synaptonemal complex central region modulates crossover pathways and feedback control of meiotic double-strand break formation.
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DOI:
10.1093/nar/gkab566
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发表时间:
2021-07-21
影响因子:
14.9
通讯作者:
Kim KP
Kim KP
中科院分区:
生物学2区
文献类型:
--
作者:
Lee MS;Higashide MT;Choi H;Li K;Hong S;Lee K;Shinohara A;Shinohara M;Kim KP

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联会复合体(SC)是一种蛋白质结构,在减数分裂过程中介导同源接合和遗传重组。在芽殖酵母中,Zip-Mer-Msh(ZMM)蛋白促进交换(CO)形成并启动SC形成。在SC延长过程中,SUMO化的SC组分Ecm 11和Ecm 11相互作用蛋白Gmc 2促进SC中心区组分Zip 1的聚合。通过物理重组、细胞学和遗传学分析,我们发现ecm 11和gmc 2突变体在减数分裂重组中表现出染色体特异性缺陷。CO频率在短染色体(染色体III)减少,而CO和非交叉频率在长染色体(染色体VII)升高。此外,在ecm 11和gmc 2突变体中,更多的双链断裂(DSB)形成在一个长的染色体在后期前期I,这意味着Ecm 11-Gmc 2(EG)复合物参与DSB形成的稳态调节。EG复合物可以参与接合分子(JM)加工和/或用于ZMM依赖性CO指定重组的双霍利迪结解析。EG复合物的缺乏改善了zmm突变体中JM加工缺陷,表明EG复合物在抑制ZMM非依赖性重组中发挥作用。我们的研究结果表明,SC中心区域的功能作为一个隔间隔离重组相关蛋白,以调节减数分裂重组过程中的特异性。
The synaptonemal complex (SC) is a proteinaceous structure that mediates homolog engagement and genetic recombination during meiosis. In budding yeast, Zip-Mer-Msh (ZMM) proteins promote crossover (CO) formation and initiate SC formation. During SC elongation, the SUMOylated SC component Ecm11 and the Ecm11-interacting protein Gmc2 facilitate the polymerization of Zip1, an SC central region component. Through physical recombination, cytological, and genetic analyses, we found that ecm11 and gmc2 mutants exhibit chromosome-specific defects in meiotic recombination. CO frequencies on a short chromosome (chromosome III) were reduced, whereas CO and non-crossover frequencies on a long chromosome (chromosome VII) were elevated. Further, in ecm11 and gmc2 mutants, more double-strand breaks (DSBs) were formed on a long chromosome during late prophase I, implying that the Ecm11–Gmc2 (EG) complex is involved in the homeostatic regulation of DSB formation. The EG complex may participate in joint molecule (JM) processing and/or double-Holliday junction resolution for ZMM-dependent CO-designated recombination. Absence of the EG complex ameliorated the JM-processing defect in zmm mutants, suggesting a role for the EG complex in suppressing ZMM-independent recombination. Our results suggest that the SC central region functions as a compartment for sequestering recombination-associated proteins to regulate meiosis specificity during recombination.
ECM11-GMC2复合物通过在发芽酵母中的横向丝组装来促进突发型复合物的形成。
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