Molecular mechanisms on which Ki-67 contributes to the organization of mitotic chromosomes

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K07399
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Takagi Masatoshi 国立研究開発法人理化学研究所, 開拓研究本部, 専任研究員 (60324779)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 分裂期染色体 / Ki-67抗原 / コンデンシン

Outline of Final Research Achievements

To examine the respective roles of Ki-67 and condensins in mitotic chromosome assembly, we generated a set of HCT116-based cell lines expressing Ki-67 and/or condensin subunits that were fused with an auxin-inducible degron for their conditional degradation. Both the localization and the dynamic behavior of Ki-67 on mitotic chromosomes were not largely affected upon depletion of condensin subunits, and vice versa. When both Ki-67 and SMC2 (a core subunit of condensins) were depleted, ball-like chromosome clusters with no sign of discernible thread-like structures were observed. This severe defective phenotype was distinct from that observed in cells depleted of either Ki-67 or SMC2 alone. Our results show that Ki-67 and condensins, which localize to the external surface and the central axis of mitotic chromosomes, respectively, have independent yet cooperative functions in supporting the structural integrity of mitotic chromosomes.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

「分裂期染色体がどのような機構で構築されるか」は、古くから細胞生物学の重要課題の一つであるが未だ十分に解明されていない。従来はコンデンシン複合体を中心に解析が進められてきたが、そこに本研究で注目するKi67抗原の解析を融合することで、課題解明に向けた新たな展開が期待される。本研究成果はKi67抗原とコンデンシン複合体の機能的関係性についての基礎的な知見を多く含むものであり、今後の研究の礎になるという点で学術的意義がある。