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静止期着丝粒组装与拆卸的动力学

The dynamics of centromere assembly and disassembly during quiescence.

作者信息

Marescal Océane, Su Kuan-Chung, Moodie Brittania, Taylor Noah J L, Cheeseman Iain M

出版信息

bioRxiv. 2025 Sep 8:2025.09.08.674938. doi: 10.1101/2025.09.08.674938.

Abstract

Quiescence is a state in which cells undergo a prolonged proliferative arrest while maintaining their capacity to reenter the cell cycle. Here, we analyze entry and exit from quiescence, focusing on how cells regulate the centromere, a structure involved in chromosome segregation. Despite the constitutive localization of centromere proteins throughout the cell cycle, we find that cells rapidly disassemble most centromere proteins during quiescence entry, while preserving those required to maintain centromere identity. During quiescence exit, the centromere is reassembled and rapidly regains normal homeostatic levels of centromere proteins. Although the histone variant CENP-A is typically deposited during G1, we find that CENP-A deposition does not occur during the G1 immediately following quiescence exit, and instead occurs after cells complete their first mitosis. In contrast, other centromere proteins relocalize during the first S phase independent of DNA replication. These findings reveal centromere dynamics during quiescence entry and exit and highlight paradigms for the timing and control of centromere protein deposition.

摘要

静止期是细胞经历长时间增殖停滞但仍保持重新进入细胞周期能力的一种状态。在此,我们分析静止期的进入和退出,重点关注细胞如何调控着丝粒,这是一种参与染色体分离的结构。尽管着丝粒蛋白在整个细胞周期中都有组成性定位,但我们发现细胞在进入静止期时会迅速拆解大多数着丝粒蛋白,同时保留维持着丝粒身份所需的蛋白。在静止期退出时,着丝粒会重新组装,并迅速恢复着丝粒蛋白的正常稳态水平。虽然组蛋白变体CENP - A通常在G1期沉积,但我们发现CENP - A沉积不在静止期退出后的紧接着的G1期发生,而是在细胞完成第一次有丝分裂后发生。相反,其他着丝粒蛋白在第一个S期重新定位,且与DNA复制无关。这些发现揭示了进入和退出静止期时的着丝粒动态,并突出了着丝粒蛋白沉积的时间安排和控制模式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdc8/12440008/131e6737d4aa/nihpp-2025.09.08.674938v1-f0001.jpg

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