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AID技術を利用したヒト染色体維持機構と染色体構造の関係性の解明

Publicly

Project AreaChromosome Orchestration System
Project/Area Number 18H04719
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Research InstitutionNational Institute of Genetics

Principal Investigator

鐘巻 将人  国立遺伝学研究所, 遺伝メカニズム研究系, 教授 (20444507)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Granted (Fiscal Year 2019)
Budget Amount *help
¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Keywordsオーキシンデグロン / 細胞工学 / 染色体不安定性 / 染色体構造 / SMCタンパク質 / DNA複製タイミング / 複製フォーク
Outline of Annual Research Achievements

本研究はオーキシンデグロン技術をヒト培養細胞に応用し、ヒト染色体構造と機能を解明することを目標としている

SMC5-6複合体は、そのリング状の構造からDNAをトポロジカルに捉えることで機能を果たしていると考えられるが、その明確な機能は明らかになっていない。そこで、SMC5-6複合体の核内および染色体上における局在を、顕微鏡観察およびChIP-seqにより解析した。これら解析より、セントロメア付近にSMC5-6は多く局在し、そのほか遺伝子密度の高い領域、rDNA領域などに局在が見られた。オーキシンデグロン技術により、SMC5-6を分解除去するとS期進行に問題は起きないが、その後の分裂期に染色体分配異常が起こることが明らかになった。これが原因で細胞はDNAダメージを蓄積し、生育が悪くなる。またトポイシメラーゼIIを分解除去すると、SMC5-6の染色体結合量が大幅に上昇することから、娘染色体のカテネーションの除去にSMC5-6は寄与している可能性が考えられる。現在、SMC5-6の機能を明らかにするためのより詳細な解析を続けている。

同じくSMCファミリーに属するコヒーシンは娘染色体接合と染色体高次構造形成に寄与することが知られている。コヒーシンを構成するSMC1A, SMC3やローダーNIPBLやアンローダーWAPLに対するオーキシンデグロン株を作成した。これらを共同研究でHi-Cにより染色体高次構造への影響を調べている。そのほか複製タイミング制御に関するRIF1のデグロン株を作成し、複製タイミングが細胞周期のいつきまるか詳細な研究を進めている。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

提案した研究は全て順調に進めている。

Strategy for Future Research Activity

現在の研究を継続し、データを蓄積したのち論文公表をおこなう。また国際学会での成果発表もおこなう。

Report

(1 results)
  • 2018 Annual Research Report

Research Products

(22 results)

All 2019 2018 Other

All Int'l Joint Research Journal Article Presentation Book Remarks

  • [Int'l Joint Research] Imperial College of London(英国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Baylor College of Medicine(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] University of Copenhagen(デンマーク)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Generation of conditional auxin-inducible degron (AID) cells and tight control of degron-fused proteins using the degradation inhibitor auxinole2019

    • Author(s)
      Yesbolatova Aisha、Natsume Toyoaki、Hayashi Ken-ichiro、Kanemaki Masato T.
    • Journal Title

      Methods

      Volume: in press

    • DOI

      10.1016/j.ymeth.2019.04.010

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Temporal and Spatial Epigenome Editing Allows Precise Gene Regulation in Mammalian Cells2019

    • Author(s)
      Kuscu Cem、Mammadov Rashad、Czikora Agnes、Unlu Hayrunnisa、Tufan Turan、Fischer Natasha Lopes、Arslan Sevki、Bekiranov Stefan、Kanemaki Masato、Adli Mazhar
    • Journal Title

      Journal of Molecular Biology

      Volume: 431 Pages: 111-121

    • DOI

      10.1016/j.jmb.2018.08.001

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Chk1-mediated Cdc25A degradation as a critical mechanism for normal cell-cycle progression2019

    • Author(s)
      Goto H., Natsume T., Kanemaki M.T., Kaito A., Wang S., Gabazza E.C., Inagaki M., Mizoguchi A.
    • Journal Title

      Journal of Cell Science

      Volume: 132

    • DOI

      10.1242/jcs.223123

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Temporal Regulation of ESCO2 Degradation by the MCM Complex, the CUL4-DDB1-VPRBP Complex, and the Anaphase-Promoting Complex2018

    • Author(s)
      Minamino M, Tei S, Negishi L, Kanemaki MT, Yoshimura A, Sutani T, Bando M, Shirahige K.
    • Journal Title

      Current Biology

      Volume: 28(16) Pages: 2665-2672

    • DOI

      10.1016/j.cub.2018.06.037

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TAGing for destruction2018

    • Author(s)
      Yesbolatova Aisha、Kanemaki Masato T.
    • Journal Title

      Nature Chemical Biology

      Volume: 14 Pages: 414-415

    • DOI

      10.1038/s41589-018-0024-5

    • Related Report
      2018 Annual Research Report
    • Open Access
  • [Journal Article] Seh1 targets GATOR2 and Nup153 to mitotic chromosomes2018

    • Author(s)
      Platani Melpomeni、Samejima Itaru、Samejima Kumiko、Kanemaki Masato T.、Earnshaw William C.
    • Journal Title

      Journal of Cell Science

      Volume: 131

    • DOI

      10.1242/jcs.213140

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Replication stress induces accumulation of FANCD2 at central region of large fragile genes2018

    • Author(s)
      Okamoto Y, Iwasaki WM, Kugou K, Takahashi KK, Oda A, Sato K, Kobayashi W, Kawai H, Sakasai R, Takaori-Kondo A, Yamamoto T, Kanemaki MT, Taoka M, Isobe T, Kurumizaka H, Innan H, Ohta K, Ishiai M, Takata M.
    • Journal Title

      Nucleic Acids Res

      Volume: 46(6) Pages: 2932-2944

    • DOI

      10.1093/nar/gky058

    • NAID

      120006488604

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ligand-induced genetic degradation as a tool for target validation2018

    • Author(s)
      Yesbolatova Aisha、Tominari Yusuke、Kanemaki Masato T.
    • Journal Title

      Drug Discovery Today: Technologies

      Volume: in press

    • DOI

      10.1016/j.ddtec.2018.11.001

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [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

      J. Cell Sci.

      Volume: 131 Pages: 212092-212092

    • DOI

      10.1242/jcs.212092

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Functional analysis after rapid degradation of condensins and 3D-EM reveals chromatin volume is uncoupled from chromosome architecture in mitosis2018

    • Author(s)
      Samejima Kumiko、Booth Daniel G.、Ogawa Hiromi、Paulson James R.、Xie Linfeng、Watson Cara A.、Platani Melpomeni、Kanemaki Masato T.、Earnshaw William C.
    • Journal Title

      Journal of Cell Science

      Volume: 131

    • DOI

      10.1242/jcs.210187

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Endosomal Rab cycles regulate Parkin-mediated mitophagy.2018

    • Author(s)
      Yamano, K., Wang, C., Sarraf, S. A., Munch, C., Kikuchi, R., Noda, N. N., Hizukuri, Y., Kanemaki, M. T., Harper, W., Tanaka, K., Matsuda, N., and Youle, R. J.
    • Journal Title

      Elife

      Volume: 7

    • DOI

      10.7554/elife.31326

    • NAID

      120006457172

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dynein-Dynactin-NuMA clusters generate cortical spindle-pulling forces as a multi-arm ensemble.2018

    • Author(s)
      Okumura Masako、Natsume Toyoaki、Kanemaki Masato T、Kiyomitsu Tomomi
    • Journal Title

      eLife

      Volume: 7 Pages: 1-24

    • DOI

      10.7554/elife.36559

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Rapid protein depletion in human cells by the auxin-inducible degron technology2018

    • Author(s)
      Masato Kanemaki
    • Organizer
      NIG International Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A non-canonical DNA replication important for genome maintenance2018

    • Author(s)
      Masato Kanemaki
    • Organizer
      Okazaki Fragment Memorial Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Book] 生物の科学遺伝 ヒト疾患とモデル生物:ヒト培養細胞を用いた解析2018

    • Author(s)
      鐘巻将人
    • Total Pages
      5
    • Publisher
      エヌ・ティー・エス
    • Related Report
      2018 Annual Research Report
  • [Book] 実験医学 2018年 6月号:抗体による内在性タンパク質分解除去2018

    • Author(s)
      鐘巻将人
    • Total Pages
      2
    • Publisher
      羊土社
    • Related Report
      2018 Annual Research Report
  • [Book] 実験医学 2018年 12月号:複製フォークの異常が自己炎症性疾患を引き起こす2018

    • Author(s)
      鐘巻将人
    • Total Pages
      2
    • Publisher
      羊土社
    • Related Report
      2018 Annual Research Report
  • [Remarks] 世界初!光で細胞分裂装置の操作に成功 ~体作りに重要な細胞分裂の仕組みの理解促進に期待~

    • URL

      https://www.nig.ac.jp/nig/ja/2018/07/research-highlights_ja/20180709.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 遺伝子が転写される際のDNAの「動き」を生きた細胞の中で捉えた!

    • URL

      https://www.nig.ac.jp/nig/ja/2019/03/research-highlights_ja/20190305.html

    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2019-12-27  

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