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Regulation of the initiation of base excision repair by the protein-protein interactions

Research Project

Project/Area Number 25340036
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Risk sciences of radiation and chemicals
Research InstitutionOsaka Prefecture University

Principal Investigator

KUBO KIHEI  大阪府立大学, 生命環境科学研究科(系), 教授 (40117619)

Co-Investigator(Kenkyū-buntansha) Takenaka Shigeo  大阪府立大学, 生命環境科学研究科, 准教授 (10280067)
YAMAMOTO RYOHEI  大阪府立大学, 生命環境科学研究科, 講師 (20457998)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords塩基除去修復 / DSB / MPG / PIKK / RPA2 / タンパク質相互作用 / ノックダウン / Pol beta / APEX / タンパク質間相互作用 / p53 / ATM / AP site / DNA損傷 / DNA修復 / マウス胎児線維芽細胞 / HeLa細胞 / ノックダウン細胞 / 脱塩基部位 / 修復複合体 / DNA修復制御 / グリコシラーゼ
Outline of Final Research Achievements

The regulation of initiation of base excision repair (BER) by MPG was investigated using mouse embryonic fibroblasts (MEF). In growth-arrested MEF, the excision of MMS-induced methylated bases was greatly suppressed while the sensitivity was significantly lower as compared with growing cells. The APEX protein content was reduced in growth-arrested MEF or PolB-deficient MEFs. Furthermore, MPG was also decreased in these cells. After the immunoprecipitation with FLAG-tagged MPG, co-precipitated proteins were analyzed by LC/MS/MS and 13 novel proteins were identified. After MMS-treatment, the enhanced interactions with 7 proteins including MLH1, a DnaJ homolog protein and proteasome-related proteins were observed, while the interaction with 5 proteins including Hsc70 were unchanged. Reduced interaction of MPG with RPA2 and increased interaction with p53 suggest that the production of DSB as a result of BER altered protein interaction with MPG via activation of PIKK.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (16 results)

All 2015 2014 2013

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (11 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Abundance of BER-related proteins depends on the cellular proliferation status and presence of DNA polymerase β2015

    • Author(s)
      Yamamoto, M., Yamamoto, R., Takenaka, S., Matsuyama, S., Kubo, K.
    • Journal Title

      Jounal of Radiation Research

      Volume: 56 Issue: 4 Pages: 707-712

    • DOI

      10.1093/jrr/rrv010

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] AP endonuclease knockdown enhances methyl methanesulfonate hypersensitivity of DNA polymerase β knockout mouse embryonic fibroblast2015

    • Author(s)
      Yamamoto, R., Umetsu, M., Yamamoto, M., Matsuyama, S., Takenaka, S., Ide, H., Kubo, K.
    • Journal Title

      Jounal of Radiation Research

      Volume: 56 Issue: 3 Pages: 462-466

    • DOI

      10.1093/jrr/rru125

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Profiling of plasma metabolites in canine oral melanoma using gas chromatography-mass spectrometry2015

    • Author(s)
      Kawabe M, Baba Y, Tamai R, Yamamoto R, Komori M, Mori T, Takenaka S.
    • Journal Title

      Journal of veterinary Medical Science

      Volume: 77 Pages: 1025-8

    • NAID

      130005094686

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] マウス細胞におけるメチル化損傷に対するBER機構について2015

    • Author(s)
      山本亮平、山本瑞希、久保喜平
    • Journal Title

      放射線生物研究

      Volume: 50 Pages: 226-241

    • NAID

      40020691898

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hypersensitivity of mouse NEIL1-knockdown cells to hydrogen peroxide during S phase2014

    • Author(s)
      Ryohei Yamamoto
    • Journal Title

      Journal of Radiation Research

      Volume: in press Issue: 4 Pages: 707-712

    • DOI

      10.1093/jrr/rru021

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] メチル化剤がマウスMPGの物理的相互作用に及ぼす影響の検討2015

    • Author(s)
      山本瑞樹、松山聡、久保喜平、山本亮平、竹中重雄
    • Organizer
      日本放射線影響学会ワークショップ
    • Place of Presentation
      富山大学黒田講堂(富山市)
    • Year and Date
      2015-10-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] マウス胎児線維芽細胞におけるDNA polymerase β knockoutとAP endonuclease I knockdownのアルキル化損傷修復への影響2015

    • Author(s)
      中山裕美、山本亮平、松山聡、久保喜平
    • Organizer
      日本放射線影響学会ワークショップ
    • Place of Presentation
      富山大学黒田講堂(富山市)
    • Year and Date
      2015-10-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] Abundance of BER-related proteins depends on cell proliferation status and the presence of DNA polymerase β2015

    • Author(s)
      Yamamoto, M., Yamamoto, R., Takenaka, S., Matsuyama, S. and Kubo, K.
    • Organizer
      15th international congress of radiation research
    • Place of Presentation
      国立京都国際会館(京都市左京区)
    • Year and Date
      2015-05-25
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] DNA polymerase β knockoutマウス胎児線維芽細胞におけるAP endonuclease knockdownによるメチル化剤感受性の影響2014

    • Author(s)
      山本亮平、梅津万記大、山本瑞希、松山聡、久保喜平
    • Organizer
      日本放射線影響学会第57回大会
    • Place of Presentation
      かごしま県民交流センター(鹿児島県・鹿児島市)
    • Year and Date
      2014-10-01 – 2014-10-03
    • Related Report
      2014 Research-status Report
  • [Presentation] Methypurine DNA glycosylaseとその関連タンパク量は細胞の増殖状態およびDNA polymerase βの有無に影響される2014

    • Author(s)
      山本瑞希、山本亮平、竹中重雄、松山聡、久保喜平
    • Organizer
      日本放射線影響学会第57回大会
    • Place of Presentation
      かごしま県民交流センター(鹿児島県・鹿児島市)
    • Year and Date
      2014-10-01 – 2014-10-03
    • Related Report
      2014 Research-status Report
  • [Presentation] DNA polymeraseβ knockoutマウス胎児線維芽細胞におけるAP endonuclease knockdownによるメチル化剤感受性の変化2014

    • Author(s)
      山本亮平、梅津万記大、松山聡、久保喜平
    • Organizer
      第157回日本獣医学会学術集会
    • Place of Presentation
      北海道大学(北海道・札幌市)
    • Year and Date
      2014-09-09 – 2014-09-12
    • Related Report
      2014 Research-status Report
  • [Presentation] 細胞の増殖状態およびDNA polymerase β(Polβ)の存在が他のBER関連タンパク量に与える影響2014

    • Author(s)
      山本瑞希、山本亮平、竹中重雄、松山聡、久保喜平
    • Organizer
      第157回日本獣医学会学術集会
    • Place of Presentation
      北海道大学(北海道・札幌市)
    • Year and Date
      2014-09-09 – 2014-09-12
    • Related Report
      2014 Research-status Report
  • [Presentation] マウスDNA polymerase β knockout細胞におけるFlap endonuclease 1 knockdownのアルキル化損傷修復への影響2014

    • Author(s)
      鈴木紘史、山本亮平、松山聡、久保喜平
    • Organizer
      第157回日本獣医学会学術集会
    • Place of Presentation
      北海道大学(北海道・札幌市)
    • Year and Date
      2014-09-09 – 2014-09-12
    • Related Report
      2014 Research-status Report
  • [Presentation] マウスMPGの単離精製と特性解析2013

    • Author(s)
      橋本 拓磨、永野 綾子、山本 亮平、松山 聡、久保 喜平
    • Organizer
      第156回日本獣医学会学術集会
    • Place of Presentation
      岐阜市
    • Related Report
      2013 Research-status Report
  • [Presentation] マウス胎児線維芽細胞におけるAPE1 knockdownによるアルキル化損傷修復への影響2013

    • Author(s)
      山田 彩容子、梅津 万記大、山本 亮平、松山 聡、久保 喜平
    • Organizer
      第156回日本獣医学会学術集会
    • Place of Presentation
      岐阜市
    • Related Report
      2013 Research-status Report
  • [Presentation] Neil1ノックダウンマウス細胞の細胞周期による過酸化水素感受性の差2013

    • Author(s)
      山本亮平、大城由香利、下谷竜彦、松山 聡、久保喜平
    • Organizer
      日本放射線影響学会第56回大会
    • Place of Presentation
      青森市
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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