Mechanism of condensin I's action in mitotic chromosome assembly

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K06499
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43010:Molecular biology-related
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Kinoshita Kazuhisa 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 (60447886)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 染色体 / 細胞周期 / 細胞分裂

Outline of Final Research Achievements

Condensin I is a five-subunit protein complex that plays a central role in mitotic chromosome assembly in eukaryotic cells. By using Xenopus egg extracts as a functional assay, we find that condensin I complexes harboring mutations in its kleisin subunit CAP-H produce chromosomes with confined axes in the presence of topoisomerase II and highly compact structures (termed “beans”) with condensin-positive central cores in its absence. The SMC ATPase cycle and CAP-D2 are essential for such hyper-compaction. Loop extrusion activities of the mutant complexes cannot explain the chromosomal defects they exhibit in Xenopus egg extracts, implying that a loop extrusion-independent mechanism contributes to condensin I-mediated chromosome assembly and shaping.

Free Research Field

分子生物学　細胞生物学

Academic Significance and Societal Importance of the Research Achievements

分裂期染色体の構築のメカニズムは、そのプロセス自体が細胞の生存に必須であるという本質的な性質のために解析方法が限られており未解明のままであった。本研究成果の意義は、技術的困難を克服し染色体構築に中心的役割を担うコンデンシンの分子作用機構を詳細に明らかにした点にある。本研究独自のアプローチによって新たに示された分子活性を組み入れた染色体構築の分子モデルを提唱しており、今後さらなる研究の発展が期待される。