Kinesin-7 CENP-E mediates centrosome organization and spindle assembly to regulate chromosome alignment and genome stability

IF 5.9 1区 生物学 Q2 CELL BIOLOGY
Jie Chen, Shan Wu, Jie-Jie He, Yu-Peng Liu, Zhao-Yang Deng, Han-Kai Fang, Jian-Fan Chen, Ya-Lan Wei, Zhen-Yu She
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Abstract

Chromosome congression and alignment are essential for cell cycle progression and genomic stability. Kinesin-7 CENP-E, a plus-end-directed kinesin motor, is required for chromosome biorientation, congression and alignment in cell division. However, it remains unclear how chromosomes are aligned and segregated in the absence of CENP-E in mitosis. In this study, we utilize the CRISPR-Cas9 gene editing method and high-throughput screening to establish CENP-E knockout cell lines and reveal that CENP-E deletion results in defects in chromosome congression, alignment and segregation, which further promotes aneuploidy and genomic instability in mitosis. Both CENP-E inhibition and deletion lead to the dispersion of spindle poles, the formation of the multipolar spindle and spindle disorganization, which indicates that CENP-E is necessary for the organization and maintenance of spindle poles. In addition, CENP-E heterozygous deletion in spleen tissues also leads to the accumulation of dividing lymphocytes and cell cycle arrest in vivo. Furthermore, CENP-E deletion also disrupts the localization of key kinetochore proteins and triggers the activation of the spindle assembly checkpoint. In summary, our findings demonstrate that CENP-E promotes kinetochore-microtubule attachment and spindle pole organization to regulate chromosome alignment and spindle assembly checkpoint during cell division.

Abstract Image

Abstract Image

驱动蛋白-7 CENP-E介导中心体组织和纺锤体组装,调节染色体排列和基因组稳定性
染色体的连接和排列对细胞周期的进展和基因组的稳定至关重要。驱动蛋白-7 CENP-E 是一种加端定向驱动蛋白马达,细胞分裂过程中染色体的生物定向、同源和排列都需要它。然而,目前还不清楚在有丝分裂过程中没有 CENP-E 的情况下染色体是如何排列和分离的。在这项研究中,我们利用CRISPR-Cas9基因编辑方法和高通量筛选技术建立了CENP-E基因敲除细胞系,并揭示了CENP-E缺失会导致染色体会聚、排列和分离缺陷,从而进一步促进有丝分裂中的非整倍体和基因组不稳定性。CENP-E抑制和缺失都会导致纺锤极分散、多极纺锤体形成和纺锤体紊乱,这表明CENP-E对纺锤极的组织和维持是必需的。此外,脾组织中 CENP-E 杂合子缺失也会导致体内分裂淋巴细胞堆积和细胞周期停滞。此外,CENP-E 基因缺失还会破坏关键动点蛋白的定位,并引发纺锤体组装检查点的激活。总之,我们的研究结果表明,CENP-E能促进动点核心-微管的附着和纺锤极的组织,从而在细胞分裂过程中调节染色体排列和纺锤体组装检查点。
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来源期刊
Cell Proliferation
Cell Proliferation 生物-细胞生物学
CiteScore
14.80
自引率
2.40%
发文量
198
审稿时长
1 months
期刊介绍: Cell Proliferation Focus: Devoted to studies into all aspects of cell proliferation and differentiation. Covers normal and abnormal states. Explores control systems and mechanisms at various levels: inter- and intracellular, molecular, and genetic. Investigates modification by and interactions with chemical and physical agents. Includes mathematical modeling and the development of new techniques. Publication Content: Original research papers Invited review articles Book reviews Letters commenting on previously published papers and/or topics of general interest By organizing the information in this manner, readers can quickly grasp the scope, focus, and publication content of Cell Proliferation.
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