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

Research Project

Project/Area Number 17K07399
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cell biology
Research InstitutionInstitute 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
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords分裂期染色体 / Ki-67抗原 / コンデンシン / 液液相分離 / オーキシン誘導性デグロン / トポイソメラーゼ / Ki67抗原 / AID
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.

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。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (8 results)

All 2020 2019 2018 2017

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (5 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] VPS72/YL1-Mediated H2A.Z Deposition Is Required for Nuclear Reassembly after Mitosis2020

    • Author(s)
      Moreno-Andres Daniel、Yokoyama Hideki、Scheufen Anja、Holzer Guillaume、Lue Hongqi、Schellhaus Anna Katharina、Weberruss Marion、Takagi Masatoshi、Antonin Wolfram
    • Journal Title

      Cells

      Volume: 9 Issue: 7 Pages: 1702-1702

    • DOI

      10.3390/cells9071702

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Generation of an antibody recognizing a set of acetylated proteins, including subunits of BAF complexes2019

    • Author(s)
      Takagi Masatoshi
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 22 Pages: 100720-100720

    • DOI

      10.1016/j.bbrep.2019.100720

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ki-67 and condensins support the integrity of mitotic chromosomes through distinct mechanisms2018

    • Author(s)
      Takagi Masatoshi、Ono Takao、Natsume Toyoaki、Sakamoto Chiyomi、Nakao Mitsuyoshi、Saitoh Noriko、Kanemaki Masato T.、Hirano Tatsuya、Imamoto Naoko
    • Journal Title

      Journal of Cell Science

      Volume: 131 Pages: 212092-212092

    • DOI

      10.1242/jcs.212092

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Ki-67抗原が分裂期染色体表層領域に局在する分子機構2020

    • Author(s)
      髙木昌俊 工樂樹洋 今本尚子
    • Organizer
      第43回日本分子生物学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Ki-67抗原が分裂期染色体構造を支持する分子機構2019

    • Author(s)
      高木昌俊
    • Organizer
      第36回染色体ワークショップ、第17回核ダイナミクス研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] How Ki-67 functions to support the architecture of mitotic chromosomes2018

    • Author(s)
      Masatoshi Takagi
    • Organizer
      EMBO | EMBL Symposium: Principles of Chromosome Structure and Function
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Ki-67 and condensins cooperates to support the architecture of mitotic chromosomes through distinct mechanisms2017

    • Author(s)
      Takagi M, Ono T, Natsume T, Sakamoto C, Nakao M, Saitoh N, Kanemaki MT, Hirano T, Imamoto N
    • Organizer
      The 2nd meeting on SMC proteins
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Ki-67 and condensing support the integrity of mitotic chromosomes through distinct mechanisms2017

    • Author(s)
      髙木昌俊、小野教夫、夏目豊彰、坂本智代美、中尾光善、斎藤典子、鐘巻将人、平野達也、今本尚子
    • Organizer
      第35回 染色体ワークショップ、第16回 核ダイナミクス研究会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2022-01-27  

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