A DNA-containing phase-separated compartment links the nuclear envelope to chromosome axes to promote homolog pairing in C. elegans

IF 12.5 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances Pub Date : 2025-10-10 DOI:10.1126/sciadv.adw5764

Ruoxi Wang, Yuqi Tian, Libo Liu, Jian-Hua Wang, Li Zhao, Yuanyuan Liu, Feifei Qi, Liangran Zhang, Jun Zhou, Meng-Qiu Dong, Jinmin Gao

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Abstract

Homologous chromosome pairing is a critical prerequisite for successful meiosis, yet the molecular mechanisms underlying this process remain elusive. In Caenorhabditis elegans, chromosome pairing centers (PCs) and PC-recruited proteins mediate homolog recognition and pairing. Here, we further dissect the molecular characteristics of this system and reveal the involvement of a phase-separated compartment in pairing. Focusing on the PC protein HIM-8, we explored its functional domains in vivo and its self-multimerizing properties in vitro. We find that the amino-terminal domain facilitates PC chromatin binding of the carboxyl-terminal domain, whereas the middle unstructured region is essential for PC association with the nuclear envelop (NE). Integrated analyses suggest that PC-NE association is mediated by a DNA-containing phase-separated compartment that is spatially distinct from, but connected to, the chromosome axis—likely through flexible linkages. We propose that homology evaluation occurs within this compartment, where direct DNA-DNA interactions could play a role.

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在秀丽隐杆线虫中，一个含有dna的相分离室将核膜与染色体轴连接起来，以促进同源配对

同源染色体配对是减数分裂成功的关键先决条件，但这一过程的分子机制尚不清楚。在秀丽隐杆线虫中，染色体配对中心（PCs）和pc募集的蛋白介导同源识别和配对。在这里，我们进一步剖析了该系统的分子特征，并揭示了相分离室在配对中的作用。以PC蛋白HIM-8为研究对象，探讨其在体内的功能域及其在体外的自聚合特性。我们发现氨基末端结构域促进了PC染色质与羧基末端结构域的结合，而中间非结构化区域对于PC与核包膜（NE）的结合至关重要。综合分析表明，PC-NE关联是由一个含有dna的相分离室介导的，该室在空间上与染色体轴不同，但与染色体轴相连，可能是通过柔性连接。我们建议同源性评估发生在这个隔室中，在那里直接的DNA-DNA相互作用可能起作用。

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来源期刊

Science Advances 综合性期刊-综合性期刊

CiteScore

21.40

自引率

1.50%

发文量

1937

审稿时长

29 weeks

期刊介绍： Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.