生物
染色质
有丝分裂
前期
染色体早凝
细胞生物学
细胞周期蛋白依赖激酶1
染色体
形态发生
细胞周期
遗传学
细胞
减数分裂
DNA
基因
作者
Xavier Robellet,Yogitha Thattikota,Fang Wang,Tse-Luen Wee,Mirela Pascariu,Sahana Shankar,Éric Bonneil,Claire M. Brown,Damien D’Amours
出处
期刊:Genes & Development
[Cold Spring Harbor Laboratory]
日期:2015-02-15
卷期号:29 (4): 426-439
被引量:44
标识
DOI:10.1101/gad.253294.114
摘要
The initiation of chromosome morphogenesis marks the beginning of mitosis in all eukaryotic cells. Although many effectors of chromatin compaction have been reported, the nature and design of the essential trigger for global chromosome assembly remain unknown. Here we reveal the identity of the core mechanism responsible for chromosome morphogenesis in early mitosis. We show that the unique sensitivity of the chromosome condensation machinery for the kinase activity of Cdk1 acts as a major driving force for the compaction of chromatin at mitotic entry. This sensitivity is imparted by multisite phosphorylation of a conserved chromatin-binding sensor, the Smc4 protein. The multisite phosphorylation of this sensor integrates the activation state of Cdk1 with the dynamic binding of the condensation machinery to chromatin. Abrogation of this event leads to chromosome segregation defects and lethality, while moderate reduction reveals the existence of a novel chromatin transition state specific to mitosis, the intertwist configuration. Collectively, our results identify the mechanistic basis governing chromosome morphogenesis in early mitosis and how distinct chromatin compaction states can be established via specific thresholds of Cdk1 kinase activity.
科研通智能强力驱动
Strongly Powered by AbleSci AI