Regulation of condensin II by self-suppression and release mechanisms

• Published in: Molecular biology of the cell 2024-02, Vol.35 (2), p.ar21
• Main Authors: Yoshida, Makoto M, Kinoshita, Kazuhisa, Shintomi, Keishi, Aizawa, Yuuki, Hirano, Tatsuya
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphatases - genetics; Animals; Cell research; Cellular control mechanisms; Cellular proteins; Chromosomes; DNA-Binding Proteins - physiology; Mitosis; Multiprotein Complexes - genetics; Physiological aspects
• ISSN: 1059-1524; 1939-4586; 1939-4586
• DOI: 10.1091/mbc.E23-10-0392

In vertebrates, two distinct condensin complexes, condensin I and condensin II, cooperate to drive mitotic chromosome assembly. It remains largely unknown how the two complexes differentially contribute to this process at a mechanistic level. We have previously dissected the role of individual subunits of condensin II by introducing recombinant complexes into egg extracts. Here we extend these efforts by introducing a modified functional assay using extracts depleted of topoisomerase IIα (topo IIα), which allows us to further elucidate the functional similarities and differences between condensin I and condensin II. The intrinsically disordered C-terminal region of the CAP-D3 subunit (the D3 C-tail) is a major target of Cdk1 phosphorylation, and phosphorylation-deficient mutations in this region impair condensin II functions. We also identify a unique helical structure in CAP-D3 (the D3 HEAT docker) that is predicted to directly interact with CAP-G2. Deletion of the D3 HEAT docker, along with the D3 C-tail, enhances the ability of condensin II to assemble mitotic chromosomes. Taken together, we propose a self-suppression mechanism unique to condensin II that is released by mitotic phosphorylation. Evolutionary implications of our findings are also discussed.