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2019 Fiscal Year Annual Research Report

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 Offered Research

Project AreaChromosome Orchestration System
Project/Area Number 18H04719
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
Keywordsゲノム維持 / DNA複製 / デグロン / 染色体
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複合体に対するオーキシンデグロン変異細胞を作成し詳細な解析を行った。その結果、SMC5-6複合体の除去は染色体不安定生と分配異常を引き起こし、DNAダメージやp53の活性化を引き起こすことをしめした。さらに、染色体部分配異常は、直前のS期とG2期にSMC5-6が欠損していると、引き起こされることをみいだした。これら結果をまとめて論文発表した(Bueno Venegas et al. Cell Reports, 2020)。

並行して、複製関連因子MCM8-9の機能解析を継続している。複製ヘリカーゼMCM2にオーキシンデグロンタグを導入し、S期にMCM2を分解すると、MCM8-9に依存したDNA合成が観察される。このDNA合成には相同組換えが関与しているが、そこに新規因子HROBが必要であることを見出した。HROBとMCM8-9は同一の経路で、DNA未複製領域を複製するのに機能すると考えられる。またHROBとMCM8-9は減数分裂組換えにも関与することを見出した。これら結果を論文発表した(Hudest et al., Genes and Development, 2019)。

Research Progress Status

令和元年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和元年度が最終年度であるため、記入しない。

  • Research Products

    (19 results)

All 2020 2019 Other

All Int'l Joint Research (4 results) Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 6 results) Presentation (5 results) (of which Int'l Joint Research: 4 results,  Invited: 4 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] University of Aberdeen/University college of London(英国)

    • Country Name
      UNITED KINGDOM
    • Counterpart Institution
      University of Aberdeen/University college of London
  • [Int'l Joint Research] Stony Brook University/Baylor College of Medicine(米国)

    • Country Name
      U.S.A.
    • Counterpart Institution
      Stony Brook University/Baylor College of Medicine
  • [Int'l Joint Research] University of Denmark(デンマーク)

    • Country Name
      DENMARK
    • Counterpart Institution
      University of Denmark
  • [Int'l Joint Research] University of Toronto(カナダ)

    • Country Name
      CANADA
    • Counterpart Institution
      University of Toronto
  • [Journal Article] Inducible Degradation of the Human SMC5/6 Complex Reveals an Essential Role Only during Interphase2020

    • Author(s)
      Venegas Andres Bueno、Natsume Toyoaki、Kanemaki Masato、Hickson Ian D.
    • Journal Title

      Cell Reports

      Volume: 31 Pages: 107533~107533

    • DOI

      https://doi.org/10.1016/j.celrep.2020.107533

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cyclin A triggers Mitosis either via the Greatwall kinase pathway or Cyclin B2020

    • Author(s)
      Hegarat Nadia、Crncec Adrijana、Suarez Peredo Rodriguez Maria F、Echegaray Iturra Fabio、Gu Yan、Busby Oliver、Lang Paul F、Barr Alexis R、Bakal Chris、Kanemaki Masato T、Lamond Angus I、Novak Bela、Ly Tony、Hochegger Helfrid
    • Journal Title

      The EMBO Journal

      Volume: e104419 Pages: e104419

    • DOI

      https://doi.org/10.15252/embj.2020104419

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] UBC13-Mediated Ubiquitin Signaling Promotes Removal of Blocking Adducts from DNA Double-Strand Breaks2020

    • Author(s)
      Akagawa Remi、Trinh Hai Thanh、Saha Liton Kumar、Tsuda Masataka、Hirota Kouji、Yamada Shintaro、Shibata Atsushi、Kanemaki Masato T.、Nakada Shinichiro、Takeda Shunichi、Sasanuma Hiroyuki
    • Journal Title

      iScience

      Volume: 23 Pages: 101027~101027

    • DOI

      https://doi.org/10.1016/j.isci.2020.101027

    • Peer Reviewed / Open Access
  • [Journal Article] Control of homologous recombination by the HROB-MCM8-MCM9 pathway2019

    • Author(s)
      Hustedt Nicole、Saito Yuichiro、Zimmermann Michal、Alvarez-Quilon Alejandro、Setiaputra Dheva、Adam Salom?、McEwan Andrea、Yuan Jing Yi、Olivieri Michele、Zhao Yichao、Kanemaki Masato T.、Jurisicova Andrea、Durocher Daniel
    • Journal Title

      Genes & Development

      Volume: 33 Pages: 1397~1415

    • DOI

      10.1101/gad.329508.119

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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: 164-165 Pages: 73~80

    • DOI

      https://doi.org/10.1016/j.ymeth.2019.04.010

    • Peer Reviewed / Open Access
  • [Journal Article] Auxin-mediated rapid degradation of target proteins in hippocampal neurons2019

    • Author(s)
      Nakano Risako、Ihara Naoki、Morikawa Shota、Nakashima Ai、Kanemaki Masato T.、Ikegaya Yuji、Takeuchi Haruki
    • Journal Title

      NeuroReport

      Volume: 30 Pages: 908~913

    • DOI

      https://doi.org/10.1097/WNR.0000000000001299

    • Peer Reviewed
  • [Journal Article] HsSAS-6-dependent cartwheel assembly ensures stabilization of centriole intermediates2019

    • Author(s)
      Yoshiba Satoko、Tsuchiya Yuki、Ohta Midori、Gupta Akshari、Shiratsuchi Gen、Nozaki Yuka、Ashikawa Tomoko、Fujiwara Takahiro、Natsume Toyoaki、Kanemaki Masato T.、Kitagawa Daiju
    • Journal Title

      Journal of Cell Science

      Volume: 132 Pages: 217521~217521

    • DOI

      https://doi.org/10.1242/jcs.217521

    • Peer Reviewed / Open Access
  • [Journal Article] Ligand-induced genetic degradation as a tool for target validation2019

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

      Drug Discovery Today: Technologies

      Volume: 31 Pages: 91~98

    • DOI

      https://doi.org/10.1016/j.ddtec.2018.11.001

    • Peer Reviewed
  • [Presentation] The Auxin-Inducible Degron (AID) system as a tool for target validation2019

    • Author(s)
      Masato Kanemaki
    • Organizer
      TPD Forum Japan
    • Int'l Joint Research / Invited
  • [Presentation] MCMBP is an MCM chaperon protecting the MCM subunits from degradation2019

    • Author(s)
      Masato Kanemaki
    • Organizer
      CSHL meeting on eukaryotic DNA replication and genome maintenance
    • Int'l Joint Research / Invited
  • [Presentation] Auxin-inducible degron (AID) technology for rapid protein depletion in human cells2019

    • Author(s)
      Masato Kanemaki
    • Organizer
      日本遺伝学会 国際シンポジウム
    • Int'l Joint Research / Invited
  • [Presentation] The Auxin-Inducible Degron (AID) system as a tool for target validation2019

    • Author(s)
      Masato Kanemaki
    • Organizer
      TPD summit in Boston
    • Int'l Joint Research / Invited
  • [Presentation] MCMBP is an MCM chaperon protecting the MCM subunits from degradation2019

    • Author(s)
      鐘巻将人
    • Organizer
      3Rワークショップ
  • [Remarks] MCM8–9経路の相同組換えを制御する新規因子HROB

    • URL

      https://www.nig.ac.jp/nig/ja/2019/09/research-highlights_ja/rh20190911.html

  • [Patent(Industrial Property Rights)] オーキシンデグロンシステムのキット、およびその使用2019

    • Inventor(s)
      鐘巻将人、林謙一郎
    • Industrial Property Rights Holder
      大学共同利用機 関法人情報・シ ステム研究機
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      特願2019-131464

URL: 

Published: 2021-01-27  

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