Modeling the functions of condensin in chromosome shaping and segregation

Yuji Sakai; Atsushi Mochizuki; Kazuhisa Kinoshita; Tatsuya Hirano; Masashi Tachikawa

doi:10.1371/journal.pcbi.1006152

Modeling the functions of condensin in chromosome shaping and segregation

PLoS Comput Biol. 2018 Jun 18;14(6):e1006152. doi: 10.1371/journal.pcbi.1006152. eCollection 2018 Jun.

Authors

Yuji Sakai^{1

2

3}, Atsushi Mochizuki^{1

2

4

5}, Kazuhisa Kinoshita⁶, Tatsuya Hirano⁶, Masashi Tachikawa^{1

2

4}

Affiliations

¹ iTHES Research Group, RIKEN, Wako, Japan.
² Theoretical Biology Laboratory, RIKEN, Wako, Japan.
³ Department of Biochemistry and Molecular Biology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
⁴ iTHEMS Program, RIKEN, Wako, Japan.
⁵ CREST, JST 4-1-8 Honcho, Kawaguchi, Japan.
⁶ Chromosome Dynamics Laboratory, RIKEN, Wako, Japan.

Abstract

The mechanistic details underlying the assembly of rod-shaped chromosomes during mitosis and how they segregate from each other to act as individually mobile units remain largely unknown. Here, we construct a coarse-grained physical model of chromosomal DNA and condensins, a class of large protein complexes that plays key roles in these processes. We assume that condensins have two molecular activities: consecutive loop formation in DNA and inter-condensin attractions. Our simulation demonstrates that both of these activities and their balancing acts are essential for the efficient shaping and segregation of mitotic chromosomes. Our results also demonstrate that the shaping and segregation processes are strongly correlated, implying their mechanistic coupling during mitotic chromosome assembly. Our results highlight the functional importance of inter-condensin attractions in chromosome shaping and segregation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphatases* / chemistry
Adenosine Triphosphatases* / metabolism
Chromosome Segregation / physiology*
Chromosomes* / chemistry
Chromosomes* / metabolism
Chromosomes* / ultrastructure
Computational Biology
DNA-Binding Proteins* / chemistry
DNA-Binding Proteins* / metabolism
Humans
Models, Genetic
Molecular Dynamics Simulation
Multiprotein Complexes* / chemistry
Multiprotein Complexes* / metabolism

Substances

DNA-Binding Proteins
Multiprotein Complexes
condensin complexes
Adenosine Triphosphatases

Grants and funding

This work was partially supported by the Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research [15K06959 to KK, 15H05971 to TH and 16H01454 to MT], and a Pioneering Project at RIKEN (to AM and TH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.