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Regulatory mechanism for initiating yeast mitochondrial DNA recombination-driven reolication upon nuclear DNA damage

Research Project

Project/Area Number 26440013
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Molecular biology
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

LING Feng  国立研究開発法人理化学研究所, 吉田化学遺伝学研究室, 専任研究員 (70281665)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords組換え / チェックポイント / ミトコンドリア / 活性酸素種( / ミトコンドリアDNA / DNA二重鎖切断 / DNA損傷修復 / 出芽酵母 / ロ-リングサークル型複製 / ホモプラスミー / コンカテマー / 細胞周期 / チェック・ポイント活性化 / 相同DNA対合 / 活性酸素種 / ROSスカンベンジャー / 5’ー3’エキソヌクレアーゼ
Outline of Final Research Achievements

Activation of the Mec1/Rad53 checkpoint pathway increases mtDNA copy number. The significance of induced mtDNA replication during the checkpoint remains unclear.
In the current project, we found that mtDNA level increase upon checkpoint activation is dependent on Mhr1 and independent of Abf2. We detected lower mitotic recombination rates in rad52-null cells, but not in rad51-null cells. Rho0 or mhr1-1 cells had lower mitotic recombination rates. The increased rate of mitotic recombination in rrm3-null cells was diminished by mhr1-1. MtDNA level in mhr1-1 was half that of wild-type cells, and mhr1-1 also diminished increases in mtDNA level in mhr1-1 rad51-null or mhr1-1 rad52-null cells. Rho0 cells had the lowest survival rates at stationary phase. mhr1-1 cells also had a short lifespan, similar to that of rrm3-null, and a synergistically negative effect was observed in rrm3-null mhr1-1 cells, indicating Mhr1 is required for longevity, particularly upon checkpoint activation.

Academic Significance and Societal Importance of the Research Achievements

ミトコンドリアDNAがATP生産に必要なタンパク質サブユニットの一部をコードしている。これらのサブユニットの量がミトコンドリアDNAのコピー数の増減によって調節される。核DNAチェックポイント活性化が起き、ミトコンドリアDNAのコピー数が顕著に増加することが知られている。本研究はその機構と意義を、遺伝学的な手法を用いて出芽酵母をモデル生物として解析した。この際、mtDNAコピー数の増加はミトコンドリア組換え酵素Mhr1に依存することと、核DNAの損傷修復と寿命維持に必要であることを明らかにした。健康寿命維持におけるミトコンドリア組換えの重要性がを再認識しなくてはならないという社会的意義をもつ。

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (5 results)

All 2016 2015 2014

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (4 results)

  • [Journal Article] ROS stimulate mitochondrial allele segregation towards homoplasmy in human cells2016

    • Author(s)
      Feng Ling, Rong Niu, Hideyuki Hatakeyama, Yu-ichi Goto, Takehiko Shibata and Minoru Yoshida
    • Journal Title

      Molecular Biology of the Cell

      Volume: 27 Issue: 10 Pages: 1-10

    • DOI

      10.1091/mbc.e15-10-0690

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] A mechanism for oxidative stress-stimulated mitochondrial DNA homoplasmy2016

    • Author(s)
      Feng LING, Rong Niu, T. Shibata, Y. Goto, Hatakeyama, H., and M. Yoshida
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] A novel mechanism for human mitochondrial allele segregation towards homoplasmy2016

    • Author(s)
      Feng LING
    • Organizer
      Global Conference of Chinese Geneticists
    • Place of Presentation
      Zhejiang University, Hangzhou, Zhejiang Province, China
    • Year and Date
      2016-09-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] DNA組換えに立脚したミトコンドリア遺伝の仕組みに関する研究2015

    • Author(s)
      凌楓
    • Organizer
      柴田武彦先生古稀記念シンポジウム
    • Place of Presentation
      早稲田大学大隈会館
    • Year and Date
      2015-03-07
    • Related Report
      2014 Research-status Report
  • [Presentation] 健全なiPS細胞樹立に向けたミトコンドリア病患者細胞のmtDNAホモプラスミー化機構の解析2014

    • Author(s)
      凌楓、牛栄、小林大貴、吉田稔、畠山英之、後藤雄一
    • Organizer
      CREST 「iPS細胞」領域 研究領域ミーティング
    • Place of Presentation
      兵庫県立淡路夢舞台国際会議場
    • Year and Date
      2014-10-28 – 2014-10-29
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2020-03-30  

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