Dynamic phosphorylation of CENP-N by CDK1 guides accurate chromosome segregation in mitosis.

IF 5.3 2区生物学 Q2 CELL BIOLOGY

Journal of Molecular Cell Biology Pub Date : 2023-11-27 DOI:10.1093/jmcb/mjad041

Ran Liu, Zhen Dou, Tian Tian, Xinjiao Gao, Lili Chen, Xiao Yuan, Chunyue Wang, Jiahe Hao, Ping Gui, McKay Mullen, Felix Aikhionbare, Liwen Niu, Guoqiang Bi, Peng Zou, Xuan Zhang, Chuanhai Fu, Xuebiao Yao, Jianye Zang, Xing Liu

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Abstract

In mitosis, accurate chromosome segregation depends on the kinetochore, a supermolecular machinery that couples dynamic spindle microtubules to centromeric chromatin. However, the structure-activity relationship of the constitutive centromere-associated network (CCAN) during mitosis remains uncharacterized. Building on our recent cryo-electron microscopic analyses of human CCAN structure, we investigated how dynamic phosphorylation of human CENP-N regulates accurate chromosome segregation. Our mass spectrometric analyses revealed mitotic phosphorylation of CENP-N by CDK1, which modulates the CENP-L-CENP-N interaction for accurate chromosome segregation and CCAN organization. Perturbation of CENP-N phosphorylation is shown to prevent proper chromosome alignment and activate the spindle assembly checkpoint. These analyses provide mechanistic insight into a previously undefined link between the centromere-kinetochore network and accurate chromosome segregation.

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CDK1 对 CENP-N 的动态磷酸化引导着有丝分裂过程中染色体的准确分离。

在有丝分裂过程中，染色体的准确分离取决于动点核心，这是一种将动态纺锤体微管与中心染色质耦合在一起的超分子机械。然而，有丝分裂过程中组成型中心粒相关网络（CCAN）的结构-活性关系仍未定性。基于我们最近对人类 CCAN 结构的冷冻电镜分析，我们研究了人类 CENP-N 的动态磷酸化如何调控染色体的准确分离。我们的质谱分析发现，CDK1对CENP-N进行有丝分裂磷酸化，从而调节CENP-L-CENP-N的相互作用，以实现染色体的准确分离和CCAN的组织。CENP-N 磷酸化的扰动被证明能阻止染色体的正确排列并激活纺锤体装配检查点。这些分析从机理上揭示了中心粒-着丝点网络与染色体准确分离之间之前尚未明确的联系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Molecular Cell Biology CELL BIOLOGY-

CiteScore

9.60

自引率

1.80%

发文量

1383

期刊介绍： The Journal of Molecular Cell Biology ( JMCB ) is a full open access, peer-reviewed online journal interested in inter-disciplinary studies at the cross-sections between molecular and cell biology as well as other disciplines of life sciences. The broad scope of JMCB reflects the merging of these life science disciplines such as stem cell research, signaling, genetics, epigenetics, genomics, development, immunology, cancer biology, molecular pathogenesis, neuroscience, and systems biology. The journal will publish primary research papers with findings of unusual significance and broad scientific interest. Review articles, letters and commentary on timely issues are also welcome. JMCB features an outstanding Editorial Board, which will serve as scientific advisors to the journal and provide strategic guidance for the development of the journal. By selecting only the best papers for publication, JMCB will provide a first rate publishing forum for scientists all over the world.