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2023 Fiscal Year Final Research Report

Structural basis and dynamics of the vertebrate condensin complex responsible for mitotic chromosome condensation

Research Project

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Project/Area Number 20H03197
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 43020:Structural biochemistry-related
Research InstitutionUniversity of Shizuoka

Principal Investigator

Hara Kodai  静岡県立大学, 薬学部, 准教授 (80729343)

Co-Investigator(Kenkyū-buntansha) 橋本 博  静岡県立大学, 薬学部, 教授 (40336590)
Project Period (FY) 2020-04-01 – 2024-03-31
KeywordsX線結晶構造解析 / 染色体凝縮 / コンデンシン / HEAT-kleisin相互作用
Outline of Final Research Achievements

Condensin which mediates chromosome condensation is essential for proper chromosome segregation during mitosis. Eukaryotes, such as humans have two different types of condensin complexes, condensin I and II. These complexes share SMC subunits (SMC2-SMC4), but have different non-SMC subunits (CAP-G, D2, and H in condensin I. CAP-G2, D3, and H2 in condensin II). Our goal is to determine structures of specific non-SMC subcomplexes, such as a CAP-G/D2-H, and CAP-G2/D3-H2. These structures may reveal interactions to form non-SMC subcomplex and provide how the vertebrate condensin I functionally is distinct from condensin II. In this study, we reported (1) a crystallization of CAP-G-H bound to DNA for a structure determination by X-ray crystallography, (2) a validation of CAP-D2-H stability due to a crystallization, (3) a initial 3D map of CAP-G2-H2 for a structure determination by single-particle cryo-EM, and (4) a validation of expression vectors to produce CAP-D3-H3 recombinants.

Free Research Field

構造生物学

Academic Significance and Societal Importance of the Research Achievements

これまでSMC複合体の様々な部分構造が報告され、リング構造の形成やその開閉制御機構に関する理解が進んだ。一方で、HEATリピートサブユニットが原核生物型には存在せず、真核生物型だけに何故存在するのか、染色体動態をどのように制御しているのかは不明な点が多い。脊椎動物のコンデンシンI・IIはnon-SMCサブユニットが異なるだけで染色体の軸構造とループ領域の作り分けをどのようにして可能にするのか知ることは興味深く、真核生物が長大なゲノムDNAをどのように折りたたみ制御しているのかを知るための一助となる。さらに染色体凝縮過程を標的とした新規抗がん剤や抗菌剤の創出など、産業活用につながる。

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Published: 2025-01-30  

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