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Mechanisms for quality control of RNA in mammalian cells

Research Project

Project/Area Number 18370005
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  Fukuoka Dental College, 歯学部, Professor (00037342)

Co-Investigator(Kenkyū-buntansha) HAYAKAWA Hiroshi  Fukuoka Dental College, 歯学部, Professor (70150422)
ITO Riyoko  Fukuoka Dental College, 歯学部, Research Associate (10140865)
HIDAKA Masumi  Fukuoka Dental College, 歯学部, Associate Professor (80238310)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥17,180,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥1,980,000)
Fiscal Year 2007: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Fiscal Year 2006: ¥8,600,000 (Direct Cost: ¥8,600,000)
Keywordsoxidative stress / RNA / oxidized guanine / ribonucleotide / mouse / quality control / genetic information / expression
Research Abstract

The basal level of spontaneous errors in RNA synthesis is estimated to be 10^<-5> per residue, which is considerably higher than that for DNA replication, and the fidelity of transcription would be worse in an aerobic state. This means that numerous erroneous proteins are synthesized even in normal cells. Furthermore, the transcriptional fidelity would become lower when the RNA bases are modified by internal or external agents. Among such modifications, 8-oxoguanine (8-oxoG) is particularly important since this modified base causes base mispairing. It has been shown that the incorporation of 8-oxoG opposite the adenine residues of DNA by RNA polymerase causes a partial phenotypic suppression. In this case, although the majority of the proteins made are normal, some of the products are abnormal. Most of the erroneous proteins produced may be inactive, but some may exhibit dominant characteristics that can cause disorders of some cellular functions, which could thus lead to catastrophic consequences.
8-oxoG can be formed in RNA by the incorporation of oxidized guanine nucleotide into RNA and also by the direct oxidation of the constituent guanine base in the RNA. In E coli, the MutT protein functions to prevent the former process while the PNP protein appears to be involved in the latter. Similar mechanisms seem to function in mammalian cells, but the situations are much more complex in comparison to the bacterial ones. At least two proteins with different substrate preferences, MTH1 and NUDT5, are involved in the former process, and also two different types of proteins, PNP and YB-1, are implicated with the latter process.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (35 results)

All 2007 2006

All Journal Article (12 results) (of which Peer Reviewed: 6 results) Presentation (21 results) Book (2 results)

  • [Journal Article] Modes of action of two types of anti-neoplastic drugs,dacarbnazine and ACNU,to induce apoptosis2007

    • Author(s)
      Masayuki Sanada
    • Journal Title

      Carcinogenesis 28

      Pages: 2657-2663

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Modes of action of two types of antidrugs - drugs, dacarbazine and ACNT, to induce apoptosis.2007

    • Author(s)
      Masayuki Sanada
    • Journal Title

      Carcinogenesis 28

      Pages: 2657-2663

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Modes of action of two types of anti-neoplastic drugs, dacarbnazine and ACNU, to induce aotosis2007

    • Author(s)
      Masayuki Sanada
    • Journal Title

      Carcinogenesis 28

      Pages: 2657-2663

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular devices for high fidelity of DNA replication and gene expression2006

    • Author(s)
      Mutsuo Sekiguchi
    • Journal Title

      Proc.Japan Acad., Ser.B 52-8

      Pages: 278-296

    • NAID

      130000093838

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] A quest to understand mechanisms for genetic stability2006

    • Author(s)
      Mutsuo Sekiguchi
    • Journal Title

      DNA Repair 5

      Pages: 6750-6755

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Human polynucleotide phosphorylase protein in response to oxidative stress2006

    • Author(s)
      Hiroshi Hayakawa
    • Journal Title

      Biochemistry 45

      Pages: 6749-6755

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary 2006 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Exogenous 8-oxo-G is not utilized for nucleotide synthesis but enhances the accumulation of 8-oxo-G in DNA error-phone DNA synthesis2006

    • Author(s)
      Ja-Eun Kim
    • Journal Title

      Mutation Res. 596

      Pages: 128-136

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Molecular devices for high fidelity of DNA replication and gene expression.2006

    • Author(s)
      Mutsuo Sekiguchi
    • Journal Title

      Proc. Japan Acad., Ser. B 52

      Pages: 278-296

    • NAID

      130000093838

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] A quest to understand mechanisms for genetic stability.2006

    • Author(s)
      Mutsuo Sekiguchi
    • Journal Title

      DNA Repair 5

      Pages: 6750-6755

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Molecular devices for high fidelity of DNA replication and gene expression2006

    • Author(s)
      Mutsuo Sekiguchi
    • Journal Title

      Prc.Japan Acad., Ser.B 52・8

      Pages: 278-296

    • NAID

      130000093838

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A quest to understand molecular mechanisms for genetic stability2006

    • Author(s)
      Mutsuo Sekiguchi
    • Journal Title

      DNA Repair 5

      Pages: 750-6755

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Exogenous 8-oxo-G is not utilized for nucleotide synthesis but enhances the accumulation of 8-oxo-G in DNA through error-prone DNA synthesis2006

    • Author(s)
      Ja-Eun Kim
    • Journal Title

      Mutation Res. 596

      Pages: 128-136

    • Related Report
      2006 Annual Research Report
  • [Presentation] 酸化ヌクレオチド分解酵素における基礎質識機構の多様性の構造学的基盤2007

    • Author(s)
      有森 貴夫
    • Organizer
      第30回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-13
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] A novel gene involved in apoptosis induced by alkylated DNA damage2007

    • Author(s)
      日高 真純
    • Organizer
      第30回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-13
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] 酸化ヌクレオチド分解酵素における基質認識機構の多様性の構造学的基盤2007

    • Author(s)
      有森 貴夫
    • Organizer
      第30回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2007-12-13
    • Related Report
      2007 Annual Research Report
  • [Presentation] A new gene related to apoptosis induced by alkylated DNA damage2007

    • Author(s)
      Masumi Hidaka
    • Organizer
      66th Annun.Meeting of Japanese Cancer Assoc
    • Place of Presentation
      Yokohama,Japan
    • Year and Date
      2007-10-03
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Modes of actions of two types of antineoplastic drugs,dacarbazine and ACNU,to induce apoptosis2007

    • Author(s)
      Mutsuo Sekiguchi
    • Organizer
      66th Annun.Meeting of Japanese Cancer Assoc
    • Place of Presentation
      Yokohama,Japan
    • Year and Date
      2007-10-03
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] A new gene related to apoptosis induced by alkylated DNA damage.2007

    • Author(s)
      Nlasumi Hidaka
    • Organizer
      36th Annun. Meeting of Japanese Cancer Assoc
    • Place of Presentation
      Yokohama, japan.
    • Year and Date
      2007-10-03
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Modes of actions of two types of antineoplastic drugs,dacarbazine and ACNU,to induce aotosis2007

    • Author(s)
      Mutsuo Sekiguchi
    • Organizer
      66th Annun.Meeting of Japanese Cancer Assoc
    • Place of Presentation
      Yokohama,Japan
    • Year and Date
      2007-10-03
    • Related Report
      2007 Annual Research Report
  • [Presentation] アルキル化損傷細胞にアポトーシスを誘導する新規遺伝子の同定2007

    • Author(s)
      日高 真純
    • Organizer
      第79回遺伝学会大会
    • Place of Presentation
      岡山
    • Year and Date
      2007-09-20
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] PCNA/MutSα-mediated binding of MutLα to O^6-methylguanine-containing DNA for inducing apoptosis2007

    • Author(s)
      Masumi Hidaka
    • Organizer
      2nd Internat.Conf.on MGMT
    • Place of Presentation
      Mainz,Germany
    • Year and Date
      2007-06-15
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Roles of MGMT and MLH1 in the development of resistance to methylating anti-cancer drugs.2007

    • Author(s)
      Mutsuo Sekiguchi
    • Organizer
      2nd Internat. Conf. on MGMT
    • Place of Presentation
      Mainz, Germany.
    • Year and Date
      2007-06-15
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] PCNA/MutSα-mediated binding of MutLα to O^6-methylguanine-containing DNA for inducing apotosis2007

    • Author(s)
      Masumi Hidaka
    • Organizer
      2nd Internat.Confon MGMT
    • Place of Presentation
      Mainz,Germany
    • Year and Date
      2007-06-15
    • Related Report
      2007 Annual Research Report
  • [Presentation] Roles of MGMT and MLH1 in the development of resistance to methylating anti-cancer drugs2007

    • Author(s)
      Mutsuo Sekiguchi
    • Organizer
      2nd Internat.Conf.on MGMT
    • Place of Presentation
      Mainz,Germany
    • Year and Date
      2007-06-14
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] PCNA/MutSa-mediated binding of MutLa 06-methylguanine-containing DNA for inducing apoptosis.2007

    • Author(s)
      Nlaumi Hidaka
    • Organizer
      2nd Internat. Conf. on MGMT
    • Place of Presentation
      Mainz Germany.
    • Year and Date
      2007-06-14
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Roles of MGMT and MLH1 in the development of resistance to methylating anti-cancer drus2007

    • Author(s)
      Mutsuo Sekiguchi
    • Organizer
      2nd Internat.Conf.on MGMT
    • Place of Presentation
      Mainz,Germany
    • Year and Date
      2007-06-14
    • Related Report
      2007 Annual Research Report
  • [Presentation] Genetic stability under oxidative stress2007

    • Author(s)
      Mutsuo Sekiguchi
    • Organizer
      3rd Japan-US DNA Repair Meeting
    • Place of Presentation
      Sendai,Japan
    • Year and Date
      2007-05-08
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Mammalian proteins that act on oxidized forms of ribonucleotides and RNA2007

    • Author(s)
      Hiroshi Hayakawa
    • Organizer
      3rd Japan-US DNA Repair Meeting
    • Place of Presentation
      Sendai,Japan
    • Year and Date
      2007-05-08
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Genetic stability under oxidative stress.2007

    • Author(s)
      Mutsuo Sekiguchi
    • Organizer
      3rd Japan-US DNA Repair Meeting
    • Place of Presentation
      Sendai, Japan.
    • Year and Date
      2007-05-08
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Mammalian proteins that act on oxidized forms of ribonucleotides and RNA2007

    • Author(s)
      Hiroshi Hayakawa
    • Organizer
      3rd Japan-US DNA Repair Meeting
    • Place of Presentation
      Sendai, Japan.
    • Year and Date
      2007-05-08
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] アルキル化損傷によるアポトーシス誘導能欠損細胞の単離とその解析2006

    • Author(s)
      高木 康光
    • Organizer
      第29回日本分子生物学会
    • Place of Presentation
      名古屋
    • Year and Date
      2006-12-06
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 抗がん剤の致死作用に及ぼすミスマッチタンパク質の役割2006

    • Author(s)
      真田 正幸
    • Organizer
      第65回日癌学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2006-09-30
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] アルキル化発がんを抑制するアポトーシスの機構2006

    • Author(s)
      高木 康光
    • Organizer
      第65回日本癌学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2006-09-28
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Oxidative stress, diseases and cancer2006

    • Author(s)
      Keshav K.Singh
    • Total Pages
      1084
    • Publisher
      Imperial College Press
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Oxidative stress, diseases and cancer2006

    • Author(s)
      Keshav K. Singh
    • Total Pages
      1084
    • Publisher
      Imperial College Press
    • Related Report
      2006 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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