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Genetic system for functioning to prevent aging

Research Project

Project/Area Number 22370003
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Genetics/Genome dynamics
Research InstitutionFukuoka Dental College

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) TAKAGI Yasumitsu  福岡歯科大学, 歯学部, 准教授 (20212003)
ITO Riyoko  福岡歯科大学, 口腔歯学部, 講師 (10140865)
瀬戸山 大樹  福岡歯科大学, 歯学部, 助教 (30550850)
Project Period (FY) 2010-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2014: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2013: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2012: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2011: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2010: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
KeywordsRNA / 前駆体ヌクレオチド / 老化 / 発現異常 / 酸化ストレス / 分解酵素 / RNA結合タンパク質 / 8-オキソグアニン / 遺伝子 / 核酸 / がん / ゲノム / 酵素 / ストレス / タンパク質 / 癌 / 蛋白質
Outline of Final Research Achievements

In aerobically growing cells, in which reactive oxygen species are produced, the guanine base of RNA is oxidized to 8-oxo-7,8-dihydroguanine, which induces alterations in gene expression. Human cells contain three types of enzymes, MTH1, MTH2 and MTH3, that degrade 8-oxoguanine-containing nucleotides. In addition, the human Auf1 protein, also called HNRNPD, binds specifically to RNA containing this oxidized base and may be involved in cellular processes associated with the problems caused by RNA oxidation. Auf-deficient cells were constructed from human HeLa and Nalm-6 lines using two different targeting procedures. Both types of Auf1-deficient cells are viable, but exhibit growth retardation. The level of oxidized messenger RNA was considerably higher in Auf1-deficient cells. Auf1 may play a role in the elimination of oxidized RNA, which is required for the maintenance of proper gene expression under oxidative stress.

Report

(6 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (29 results)

All 2015 2014 2013 2012 2011 2010

All Journal Article (15 results) (of which Peer Reviewed: 15 results,  Acknowledgement Compliant: 1 results) Presentation (14 results) (of which Invited: 2 results)

  • [Journal Article] Role of Auf1 in elimination of oxidatively damaged messenger RNA in human cells2015

    • Author(s)
      Takashi Ishii, Hiroshi Hayakawa, Takeshi Sekiguchi, Noritaka Adachi, Mutsuo Sekiguchi
    • Journal Title

      Free Radical Biology and Medicine

      Volume: 79 Pages: 109-116

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [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 Annual Research 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 Annual Research Report
    • Peer Reviewed
  • [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 Annual Research 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 Annual Research 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 Annual Research 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 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of AMP-activated protein kinase by MAPO1 and FLCN inducing apoptosis triggered by alkylation mismatch in DNA2012

    • Author(s)
      T.H.Lim, R.Fujikane, S.Sano, R.Sakagami, Y.Nakatsu, T.Tsuzuki, M.Sekiguchi, M.Hidaka
    • Journal Title

      DNA Repair

      Volume: 11 Issue: 3 Pages: 259-266

    • DOI

      10.1016/j.dnarep.2011.11.006

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Diverse Substrate Recognition and Hydrolysis Mechanisms of Human NUDT52011

    • Author(s)
      Takao Arimori, at al
    • Journal Title

      Nucleic Acids Res.

      Volume: 39 Issue: 20 Pages: 8972-8983

    • DOI

      10.1093/nar/gkr575

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oxidative damage to RNA and expression patterns of MTH1 in the hippocampi of senescence-accelerated SAMP8 mice and Alzheimse's disease patients2011

    • Author(s)
      X.-N.Song, L.-Q.Zhang, D.-G.Liu, J.Lin, J.-D.Zheng, D.-P.Dai, A.-L.Hei, H.Hayakawa, M.Sekiguchi, J.-P.Cai
    • Journal Title

      Neurochem.Res.

      Volume: 36 Issue: 8 Pages: 1558-1565

    • DOI

      10.1007/s11064-011-0484-4

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular actions of E.coli MutT for control of spontaneous mutagernesis2011

    • Author(s)
      瀬戸山大樹
    • Journal Title

      Mutation Research

      Volume: 707 Pages: 9-14

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cleavage of oxidized guanine nucleotide and ADP sugar by human NUDT5 protein2011

    • Author(s)
      伊東理世子
    • Journal Title

      J.Biochem

      Volume: 149 Pages: 731-738

    • NAID

      10030585983

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human proteins that specifically bind to 8-oxoguanine-containing RNA and their responses to oxidative stress2010

    • Author(s)
      早川浩
    • Journal Title

      Biochem.Biophys.Res.Commun.

      Volume: 403 Pages: 220-224

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Roles of MutT, MTH1 and AUF1 in defence against oxidative stress2014

    • Author(s)
      Mutsuo Sekiguchi
    • Organizer
      US-Japan DNA Repair Meeting
    • Place of Presentation
      グランドエキシブ鳴門(徳島市)
    • Year and Date
      2014-10-28 – 2014-10-30
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Introduction to gene expression under oxidative stress2013

    • Author(s)
      Mutsuo Sekiguchi
    • Organizer
      第86会日本生化学会大会
    • Place of Presentation
      パシフィコ横浜(横浜市西区)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 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
    • Place of Presentation
      パシフィコ横浜(横浜市西区)
    • Related Report
      2013 Annual 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
    • 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] 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
    • 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)
      Mutsuo Sekiguchi
    • Organizer
      US-Japan DNA Repair Meeting
    • Place of Presentation
      National Conference Center, Virginia, USA
    • Related Report
      2012 Annual 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、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 Annual 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
    • Place of Presentation
      九州大学医学部
    • Related Report
      2012 Annual Research 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 Annual Research Report
  • [Presentation] Specific binding of human proteins to 8-oxoguanine-containing RNA2011

    • Author(s)
      A.Fujikane, H.Hayakawa, R.Ito, K.Nakayama, M.Sekiguchi
    • Organizer
      日本分子生物学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2011-12-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] Cleavage of oxidized nucleotides for prevention of mutation2011

    • Author(s)
      R.Ito, Y.Takagi, T.Arimori, Y.Yamagata, M.Sekiguchi, H.Hayakawa
    • Organizer
      日本分子生物学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2011-12-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] Characterization of human NUDT5 that hydrolyzes oxidized nucleotides2011

    • Author(s)
      伊東理世子、関口睦夫、山縣ゆり子、中津可道、早川浩
    • Organizer
      日本遺伝学会
    • Place of Presentation
      京都大学
    • Year and Date
      2011-09-21
    • Related Report
      2011 Annual Research Report
  • [Presentation] MTH1 prevents translational errors caused by oxidized guanine of RNA in mammalian cells2011

    • Author(s)
      蔡剣平、戴大鵬、高木康光、早川浩、関口睦夫
    • Organizer
      日本遺伝学会
    • Place of Presentation
      京都大学
    • Year and Date
      2011-09-21
    • Related Report
      2011 Annual Research Report
  • [Presentation] Human protien's specifically bound to 8-oxoagunine-containing RNA and their responses2010

    • Author(s)
      早川浩
    • Organizer
      日本分子生物学会
    • Place of Presentation
      ポートアイランド(神戸)
    • Year and Date
      2010-12-07
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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