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Biochemical analysis of Human Mre11 complex working in DNA double-strand break repair

Research Project

Project/Area Number 16K07255
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Molecular biology
Research InstitutionOsaka University (2017-2019)
Nara Institute of Science and Technology (2016)

Principal Investigator

Furukohri Asako  大阪大学, 蛋白質研究所, 准教授 (90546293)

Co-Investigator(Kenkyū-buntansha) 建部 恒  奈良先端科学技術大学院大学, 先端科学技術研究科, 助教 (00596819)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsDNA修復 / DNA二本鎖切断 / 高速AFM / 相同組換え / 二本鎖DNA切断 / Mre11
Outline of Final Research Achievements

Human MRE11-RAD50-NBS1 (MRN) complex is a central player in protecting our genome from toxic DNA damages such as DNA double-strand break. In this project, we carried out biochemical and structural analyses of human MRN complex. We found that the basic properties of human MRN and its bacterial homolog SbcCD, including their enzymatic actions and entire architectures, are mostly well-conserved among species.

Academic Significance and Societal Importance of the Research Achievements

MRN複合体はヒトの生存に必須の酵素複合体であり、ヒトのゲノムDNAの傷を修復し安定に維持するために働いている。本研究ではこのMRN複合体の蛋白質構造や酵素活性を詳細に調べ、その基礎的な知見を明らかにした。ヒトMRN複合体は発がんやがん治療のみならず、近年注目を集めるゲノム編集にも関係する重要な酵素であることから、本研究によりMRN複合体が働く仕組みの理解が深まったことは、医学・生物学的にも意義深いと考えられる。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (13 results)

All 2020 2019 2018 2017 2016 Other

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (10 results) (of which Int'l Joint Research: 1 results,  Invited: 7 results) Remarks (1 results)

  • [Journal Article] Rad50 zinc hook functions as a constitutive dimerization module interchangeable with SMC hinge2020

    • Author(s)
      Tatebe Hisashi、Lim Chew Theng、Konno Hiroki、Shiozaki Kazuhiro、Shinohara Akira、Uchihashi Takayuki、Furukohri Asako
    • Journal Title

      Nature Communications

      Volume: 11 Issue: 1 Pages: 370-370

    • DOI

      10.1038/s41467-019-14025-0

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Collision with duplex DNA renders Escherichia coli DNA polymerase III holoenzyme susceptible to DNA polymerase IV-mediated polymerase switching on the sliding clamp2017

    • Author(s)
      Thanh Thi Le, Asako Furukohri, Masahiro Tatsumi-Akiyama and Hisaji Maki
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1

    • DOI

      10.1038/s41598-017-13080-1

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Biochemical analysis of DNA polymerase actions across the trinucleotide repeats2019

    • Author(s)
      古郡 麻子
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] DNA二本鎖切断修復機構で働くヒトMRN複合体の動的構造解析2019

    • Author(s)
      古郡 麻子
    • Organizer
      第25回DNA複製・修復・組換えワークショップ
    • Related Report
      2019 Annual Research Report
  • [Presentation] DNA二本鎖切断修復機構で働くヒトMre11/Ra50/Nbs1複合体の動的構造解析2019

    • Author(s)
      古郡 麻子
    • Organizer
      第 42 回日本分子生物学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] DNA二本鎖切断修復機構で働くMre11/Ra50/Nbs1複合体の構造と機能2018

    • Author(s)
      古郡 麻子
    • Organizer
      日本遺伝学会第90回大会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] DNA二本鎖切断修復機構で働くヒトMre11/Ra50/Nbs1複合体の動的構造解析2018

    • Author(s)
      古郡 麻子
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] DNA二本鎖切断修復機構で働くMre11/Ra50/Nbs1複合体の構造と機能2018

    • Author(s)
      古郡 麻子
    • Organizer
      日本生化学会第91回大会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Biochemical analysis on nuclease activities of Mre11/Rad50 complex2017

    • Author(s)
      Asako Furukohri
    • Organizer
      IPR seminar: Chromosome dynamics and genome stability in meiosis and mitosis
    • Place of Presentation
      大阪大学蛋白質研究所、大阪府吹田市
    • Year and Date
      2017-03-23
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] DSB修復で働くMre11/Rad50複合体の生化学的解析2017

    • Author(s)
      古郡 麻子、 Chew Theng Lim、 David R.F. Leach、 真木 壽治
    • Organizer
      日本遺伝学会第89回大会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] DNA二本鎖切断修復機構で働くMre11/Rad50/Nbs1複合体の解析2017

    • Author(s)
      古郡 麻子
    • Organizer
      2017年度生命科学系学会合同年次大会(第40回日本分子生物学会年会)
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Biochemical analysis reveals a novel action of bacterial Mre11/Rad50 complex (SbcCD) at a DNA end2016

    • Author(s)
      Asako Furukohri
    • Organizer
      10th 3R International Symposium
    • Place of Presentation
      ホテル一畑、鳥取県松江市
    • Year and Date
      2016-11-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Remarks] Press Release

    • URL

      http://www.protein.osaka-u.ac.jp/wp-content/uploads/2020/02/PR_20200205.pdf

    • Related Report
      2019 Annual Research Report

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Published: 2016-04-21   Modified: 2021-02-19  

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