A high-sensitivity phospho-switch triggered by Cdk1 governs chromosome morphogenesis during cell division

Robellet, Xavier, Thattikota, Yogitha, Wang, Fang, Wee, Tse-Luen, Pascariu, Mirela, Shankar, Sahana, Bonneil, Éric, Brown, Claire M, D'Amours, Damien (February 2015) A high-sensitivity phospho-switch triggered by Cdk1 governs chromosome morphogenesis during cell division. Genes & Development, 29 (4). pp. 426-439. ISSN 0890-9369

PDF A high-sensitivity phospho-switch triggered by Cdk1 governs chromosome morphogenesis during cell division.pdf - Published Version Available under License Creative Commons Attribution. Download (2MB)

Abstract

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.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosome bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosomes, structure and function > chromosome bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosomes, structure and function bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression > phosphorylation bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression
CSHL Authors:	Wee, Tse-Luen
Communities:	CSHL labs > Spector lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	15 February 2015
Date Deposited:	04 Jan 2024 20:41
Last Modified:	04 Jan 2024 20:41
PMCID:	PMC4335297
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41383

Actions (login required)

Administrator's edit/view item