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Novel mechanisms for eliminating oxidatively damaged RNA

Research Project

Project/Area Number 24657006
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Genetics/Genome dynamics
Research InstitutionFukuoka Dental College

Principal Investigator

SEKIGUCHI Mutsuo  福岡歯科大学, 歯学部, 教授 (00037342)

Co-Investigator(Kenkyū-buntansha) SEKIGUCHI Takeshi  九州大学, 医学系研究科, 助教 (60187846)
Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsRNA / 酸化 / 遺伝子発現 / タンパク質 / 発現異常 / 酸化グアニン / 酵素 / ストレス
Research Abstract

Reactive oxygen species are produced as side products of oxygen utilization and can lead to the oxidation of nucleic acids and their precursor nucleotides. Among the various oxidized bases, 8-oxo-7,8-dihydroguanine seems to be the most critical during the transfer of genetic information because it can pair with both cytosine and adenine. During the de novo synthesis of guanine nucleotides, guanylate kinase hardly acts on an oxidized form of GMP (8-oxo-GMP) formed by the oxidation of GMP or by the cleavage of 8-oxo-GDP and 8-oxo-GTP by MutT protein. The 8-oxo-GTP produced in this way and by the oxidation of GTP can be used for RNA synthesis. This misincorporation is prevented by MutT protein, which has the potential to cleave 8-oxo-GTP as well as 8-oxo-GDP to 8-oxo-GMP. When (14)C-labeled 8-oxo-GTP was applied to CaCl2-permeabilized cells of a mutT(-) mutant strain, it could be incorporated into RNA at 4% of the rate for GTP.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (29 results)

All 2013 2012

All Journal Article (16 results) (of which Peer Reviewed: 8 results) Presentation (13 results) (of which Invited: 2 results)

  • [Journal Article] Search for proteins required for accurate gene expression under oxidative stress : Roles of guanylate kinase and RNA polymerase2013

    • Author(s)
      Hachiro Inokuchi, Riyoko Ito, Takeshi Sekiguchi, Mutsuo Sekiguchi
    • Journal Title

      J. Biol. Chem.

      Volume: 288 Pages: 32952-32962

    • Related Report
      2013 Final Research Report
  • [Journal Article] Age-dependent accumulation of 8-oxoguanine in the DNA and RNA in various rat tissues2013

    • Author(s)
      Ben Nie, Wei Gan, Fei Shi, Guo-Xin Hu, Lian-Guo Chen, Hiroshi Hayakawa, Mutsuo Sekiguchi, Jian-Ping Cai
    • Journal Title

      Oxidative Medicine and Cellular Longevity

      Volume: 2013 Pages: 1-9

    • Related Report
      2013 Final Research Report
  • [Journal Article] Elimination and utilization of oxidized guanine nucleotides in the synthesis of RNA and its precursors2013

    • Author(s)
      Takeshi Sekiguchi, Riyoko Ito, Hiroshi Hayakawa, Mutsuo Sekiguchi
    • Journal Title

      I. Biol. Chem.

      Volume: 288 Pages: 8128-8135

    • Related Report
      2013 Final Research Report
  • [Journal Article] Search for proteins required for accurate gene expression under oxidative stress: Roles of guanylate kinase and RNA polymerase2013

    • Author(s)
      Hchiro Inokuchi, Riyoko Ito, Tkeshi Sekiguchi, Mutsuo Skiguchi
    • Journal Title

      J. Biol. Chem.

      Volume: 288 Issue: 46 Pages: 32952-32962

    • DOI

      10.1074/jbc.m113.507772

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Age-dependent accumulation of 8-oxoguanine in the DNA and RNA in various rat tissues2013

    • Author(s)
      Ben Nie, Wei Gan, Fei Shi, Guo-Xin Hu, Lian-Guo Chen, Hiroshi Hayakawa, Mutsuo Sekiguchi, Jian-Ping Cai
    • Journal Title

      Oxidative medicine and Cellular Longevity

      Volume: 2013 Pages: 1-9

    • DOI

      10.1155/2013/303181

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Elimination and utilization of oxidized guanine nucleotides in the synthesis of RNA and its precursors2013

    • Author(s)
      Takeshi Sekiguchi, Riyoko Ito, Hiroshi Hayakawa, Mutsuo Sekiguchi
    • Journal Title

      J. Biol. Chem.

      Volume: 288 Pages: 8128-8135

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Stablization of MAPO1 by specific birding with folliculir and AMP-activated protein kinase in O6-methylguanine-induced apoptosis2013

    • Author(s)
      Shiori Sano, Ryuji Sakagami, Mutsuo Sekiguchi, Masumi Hidaka
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 430 Pages: 810-815

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Stabilization of MAPO1 by specific binding with follicular and AMP-activated protein kinase in O^6-methylguanine-induced apoptosis2012

    • Author(s)
      Shiori Sano, Ryuji Sakagami, Mutsuo Sekiguchi, Masumi Hidaka
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 430 Pages: 810-815

    • Related Report
      2013 Final Research Report
  • [Journal Article] The identification of novel gene, MAPO2, that is involved in the induction of apoptosis triggered by O^6-methylguanine2012

    • Author(s)
      Ryosuke Fujikane, Masayuki, Sanada, Mutsuo Sekiguchi, Masumi Hidaka
    • Journal Title

      PLoS ONE

      Volume: 7

    • Related Report
      2013 Final Research Report
  • [Journal Article] Human MTH3 (NUDT18) protein hydrolyzes oxidized forms of guanosine and deoxyguanosine diphosphate : Comparison with MTH1 and MTH22012

    • Author(s)
      Yasumitsu Takagi, Daiki Setoyama, Riyoko, Ito, Hiroshi Hayakawa, Hiroyuki Kamiya, Yuriko Yamagata, Mutsuo Sekiguchi
    • Journal Title

      J. Biol. Chem.

      Volume: 287 Pages: 21541-21549

    • Related Report
      2013 Final Research Report
  • [Journal Article] Age-dependent increasers in the oxidative damage of DNA, RNA, and their metabolites in normal and senescence-accelerated mice analyzed by LC-MS/MS : Urinary 8-oxoguanine as a novel biomarker of aging2012

    • Author(s)
      Wei Gan, Ben Nie, Fei Shi, Xin-Min Xu, Chan Qian, Yasumitsu Takagi, Hiroshi Hayakawa, Mutuo Sekiguchi, Jian-Ping Cai
    • Journal Title

      Free Radical Biology and Medicine

      Volume: 52 Pages: 1700-1707

    • Related Report
      2013 Final Research Report
  • [Journal Article] My Path toward DNA repair2012

    • Author(s)
      Mutsuo Sekiguchi
    • Journal Title

      DNA Repair

      Volume: 11 Pages: 606-615

    • Related Report
      2013 Final Research Report
  • [Journal Article] The identification of novel gene, MAPO2, that is involved in the induction of apoptosis triggered by O6-methylguanine2012

    • Author(s)
      Ryosuke Fujikane, Masauki Sanada, Mutsuo Sekiguchi, Masumi HIdaka
    • Journal Title

      PLOS ONE

      Volume: 7

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Human MTH3(NUDT18) protein hydrolyzes oxidized forms of guanosine and deoxyguanosine diphosplate: Comparison with MTH1 and MTH22012

    • Author(s)
      Yasumitsu Takagi, Daiki Setoyama, Riyoko Ito, Hiroshi Hayakawa, Hiroyuki kamiya, Yuriko Yamagata, Mutsuo Sekiguchi
    • Journal Title

      J. Biol. Chem.

      Volume: 287 Pages: 21541-21549

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Age-dependent increasers in the oxidative damage of DNA, RNA, and their metabolites in normal and senescence-accelerated mice analized by LC-MS/MS: Urinary 8-oxoguanine as a novel biomaker of aging2012

    • Author(s)
      Wei Gan, Ben Nie, Fei Shi, Xin-Min Xu, Jian-Chan Qian, Yasumitsu Takagi, Hiroshi Hayakawa, Mutsuo Sekiguchi, Jian-Ping Cai
    • Journal Title

      Free Radical Biology and Medicine

      Volume: 52 Pages: 1700-1707

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] My path toward DNA repair2012

    • Author(s)
      Mutsuo Sekiguchi
    • Journal Title

      DNA Repair

      Volume: 11 Pages: 606-615

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Introduction to gene expression under oxidative stress2013

    • Author(s)
      M. Sekiguchi
    • Organizer
      第86回日本生化学会大会
    • Related Report
      2013 Final Research Report
  • [Presentation] Translational errors caused by ROS2013

    • Author(s)
      J.-P. Cai, D.-P. Dai, H. Hayakawa, M. Sekiguchi
    • Organizer
      第86回日本生化学会大会
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] 酸素ストレス下の遺伝子発現機構2013

    • Author(s)
      井口八郎、伊東理世子、関口猛、関口睦夫
    • Organizer
      日本遺伝学会第85回大会
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] 大腸菌における8-オキソグアニンを含むヌクレオチドの排除機構2013

    • Author(s)
      伊東理世子、井口八郎、関口猛、関口睦夫
    • Organizer
      日本遺伝学会第85回大会
    • Related Report
      2013 Final Research Report
  • [Presentation] Intorduction to gene expression under oxidative stress2013

    • Author(s)
      Mutsuo Sekiguchi
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜(横浜市西区)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 大腸菌における8-オキソグアニンンを含むヌクレオチドの排除機構2013

    • Author(s)
      伊東理世子、井口八郎、関口猛、関口睦夫
    • Organizer
      日本遺伝学会
    • Place of Presentation
      慶應義塾大学日吉キャンパス(横浜市港北区)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Molecular mechanisms for accurate gene expression under oxidative stress2012

    • Author(s)
      M. Sekiguchi
    • Organizer
      US-Japan DNA Repair Meeting
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] 酸化ストレスによるRNAの異常を防ぐ酵素系2012

    • Author(s)
      伊東理世子、髙木康光、瀬戸山大樹、早川浩、関口睦夫
    • Organizer
      日本遺伝学会第84回大会
    • Related Report
      2013 Final Research Report
  • [Presentation] HeLa細胞に導入したグアニンヌクレオチドの運命2012

    • Author(s)
      関口猛、早川浩、関口睦夫
    • Organizer
      日本遺伝学会第84回大会
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] Molecular mechanisms of the induction of apoptosis to suppress mutation and cancer2012

    • Author(s)
      M. Hidaka, S. Sano, R. Fujikane, T.H. Lim, R. Sakagami, Y. Nakatsu, T. Tsuzuki, M. Sekiguchi
    • Organizer
      第35回日本分子生物学会年会
    • Related Report
      2013 Final Research Report
  • [Presentation] Molecular mechanisms for accurate gene expression under oxidative stress2012

    • Author(s)
      Mutsuo Sekiguchi
    • Organizer
      US-Japan DNA Repair Meeting
    • Place of Presentation
      National Conference Center, Virginia, USA
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 酸化ストレスによるRNAの異常を防ぐ酵素系2012

    • Author(s)
      伊東理世子、高木康光、瀬戸山大樹、早川浩、関口睦夫
    • Organizer
      日本遺伝学会第84回大会
    • Place of Presentation
      九州大学医学部
    • Related Report
      2012 Research-status Report
  • [Presentation] Molecular mechanism of the induction of apoptosis to suppress mutation and Cancer2012

    • Author(s)
      Masumi Hidaka, Shiori Sano, Ryosuke Fujikane, Teik How Lim, Ryuji Sakagami, Yoshimichi Nakatsu, Teruhisa Tsuzuki, Mutsuo Sekiguchi
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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