• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Identification and characdterization of DNA glycosylases that recognize and remove oxidative base damage in DNA

Research Project

Project/Area Number 16510035
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Risk sciences of radiation/Chemicals
Research InstitutionKyoto University

Principal Investigator

ZUANG Qiu-Mei  Kyoto University, Graduate School of Science, Associate Professor, 大学院・理学研究科, 助教授 (00260604)

Co-Investigator(Kenkyū-buntansha) YONEI Shuji  Kyoto University, Graduate School of Science, Professor, 大学院・理学研究科, 教授 (60093340)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥2,900,000 (Direct Cost: ¥2,900,000)
KeywordsIonizing radiation / Reactive oxygen species / DNA repair / Base excision repair / DNA glycosylas / Mutation / Oxidative base damage / 8-oxo-7,8-dihydroguanine / APサイト / 忠実性 / DNAポリメラーゼ / APエンドヌクレアーゼ / 塩基相補性 / DNAポリメラーゼβ / フレームシフト
Research Abstract

(1) Reactive oxygen species cause a wide variety of oxidative modifications to purines and pyrimidines in DNA. Bacteria and eukaryotes have evolved base excision repair mechanisms for oxidative base damage in DNA. E.coli has three kinds of DNA glycosylase, MutM, Nth and Nei, that recognize and remove oxidatively damaged bases from DNA. These DNA glycosylases are able to recognize and remove 5-formyluracil and 5-hydroxymethyluracil in DNA. However, several evidence showed that there are residual activities in crude extract from E.coli mutM nth nei triple mutant. In this study, we identified the abilities of novel enzyme(s) to recognize double-stranded oligonucleotides containing 5-foU. (2) 7,8-dihydro-8-oxoguanine (8-oxoG) is the most important product of oxidative base damage in DNA, and causes G:C to T:A transversions in bacteria and mammalian cells. 8-oxoG is repaired by MutM in E.coli and 8-oxoG-DNA glycosylase (Ogg1) in yeast and mammalian cells. In the present study, we identified … More and characterized an ascidian homolog of the human hOgg1 in Ciona intestinalis (CiOgg1). Introduction of the CiOgg1 gene significantly reduced the frequency of spontaneous G:C to T:A transversions in E.coli mutM mutY strain. Purified GST-CiOgg1 fusion protein had 8-oxoG DNA glycosylase/AP lyase activity. It formed Schiff base intermediates with 8-oxoG-containing duplex oligonucleotides and removed 8-oxoG preferentially from 8-oxoG/C. The CiOgg1 cleaved 8-oxoG-containing duplex DNA via β-elimination reaction. Furthermore, the expression level of CiOgg1 was compared in various tissues in Ciona intestinalis. The highest expression level was observed in testis. (3) In this study, AP endonuclease in Ciona inteslinalis (CiAPE) was purified and characterized. The properties of CiAPE were compared with those of human APE1. The CiAPE protein was about 34 kDa. It efficiently cleaved tetrahydrofuran (THF)-containing duplex oligonucleotides. In addition, the transformation of E.coli, BW9093 Δxth with CiAPE complemented the H2O2 sensitivity. These results demonstrated that CiAPE has AP endonuclease activity to prevent against oxidative stress in Ciona intestinalis. Less

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (26 results)

All 2006 2005 Other

All Journal Article (24 results) Book (2 results)

  • [Journal Article] Base excision repair fidelity in normal and cancer cells2006

    • Author(s)
      K.K.L.Chan, Q-M.Zhang, G.L.Dianov
    • Journal Title

      Mutagenesis (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cloning and characterization of an ascidian homolog of the human Ogg1 that is involved in the repair of 8-oxoG in DNA in Ciona intestinalis2006

    • Author(s)
      G.Jin, Q-M.Zhang, Y.Satou, N.Satoh, H.Kasai, S.Yonei
    • Journal Title

      International Journal of Radiation Biology 82

      Pages: 241-250

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The Shizusaccharomyces pombe homolog (SpMYH) of the Eseherichia coli MutY is required for removal of guanine from 8-oxoguanine/guanine mispairs to prevent G : C->C : G transversions2006

    • Author(s)
      T.Doi, S.Yonekura, K.Tano, S.Yonei, Q.-M.Zhang
    • Journal Title

      Journal of Radiation Research 46

      Pages: 2005-214

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cloning and characterization of an ascidian homolog of the human 8-oxoguanine DNA glycosylase (Ogg1) that is involved in the repair of 8-oxo-7.8-dihydroguanine in DNA in Ciona intestinalis2006

    • Author(s)
      G.Jin, Q.-M.Zhang, Y.Satou, N.Satoh, H.Kasai, S.Yonei
    • Journal Title

      International Journal of Radiation Biology 82

      Pages: 241-250

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cloning and characterization of an ascidian homolog of the human 8-oxoguanine DNA glycosylase (Ogg1) that is involved in the repair of 8-oxo-7,8-dihydroguanine in DNA2006

    • Author(s)
      Jin, G., Q.-M.Zhang, Y.Satou, N.Satoh, H.Kasai, S.Yonei
    • Journal Title

      International Journal of Radiation Biology 82(印刷中)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] DNA酸化への防御戦略-塩基除去修復を中心に-2005

    • Author(s)
      張秋梅, 中村允耶, 米倉慎一郎, 米井脩治
    • Journal Title

      蛋白質・核酸・酵素 50

      Pages: 322-329

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Increased sensitivity to sparsely ionizing radiation due to excessive base excision in clustered DNA damage sites in Escherichia coli2005

    • Author(s)
      P.W.Chang, Q-M.Zhang, K.Takatori, A.Tachibana, S.Yonei
    • Journal Title

      International Journal of Radiation Biology 81

      Pages: 115-123

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The Shizosaccharomyces pombe homolog (SpMYH) of the E. coli MutY is required for removal of G from 8-oxoG/G to prevent G : C-C : G transversions2005

    • Author(s)
      T.Doi, S.Yonekura, K.Tano, S.Yasuhira, S.Yonei, Q-M.Zhang
    • Journal Title

      Journal of Radiation Research 46

      Pages: 205-214

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] DNA repair fidelity of base excision repair pathways in human cell extracts2005

    • Author(s)
      Q-M.Zhang, G.L.Dianov
    • Journal Title

      DNA Repair 4

      Pages: 263-270

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] DNA glycosylase activities for thymine residues oxidized in the methyl group are functions of the hNEIL1 and hNTH1 enzymes in human cells2005

    • Author(s)
      Q.-M.Zhang, S.Yonekura, M.Takao, A.Yasui, S.Yonei
    • Journal Title

      DNA Repair 4

      Pages: 71-79

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] DNA repair fidelity of base excision repair pathways in human Cell extracts2005

    • Author(s)
      Q-M.Zhang, G.L.Dianov
    • Journal Title

      DNA Repair 4

      Pages: 263-170

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Increased sensitivity to sparsely ionizing radiation due to excessive base excision in clustered DNA damage sites in Eseheichia coli2005

    • Author(s)
      P.W.Chang, Q.-M.Zhang, K.Takatori, A.Tachibana, S.Yonei
    • Journal Title

      International Journal of Radiation Biology 81

      Pages: 115-123

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] DNA glycosylase activities for thymine residues oxidized in the methyl group are functions of the hNEIL1 and hNTH1 enzymes in human cells.2005

    • Author(s)
      Zhang, Q.-M., S.Yonekura, M.Takao, A.Yasui, H.Sugiyama, S.Yonei
    • Journal Title

      DNA Repair 4

      Pages: 71-79

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Increased sensitivity to sparsely ionizing radiation due to excessive base excision in clustered DNA damage sites in Escherichia coli.2005

    • Author(s)
      Chang, P.-W., Q.-M.Zhang, K.Takatori, A.Tachibana, S.Yonei
    • Journal Title

      International Journal of Radiation Biology 81

      Pages: 115-123

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The Shizosaccharomyces pombe homolog (SpMYH) of the Escherichia coli MutY is required for removal of guanine from 8-oxoguanine/guanine mispairs to prevent2005

    • Author(s)
      Doi, T., S.Yonekura, K.Tano, S.Yonei, Q.-M.Zhang
    • Journal Title

      Journal of Radiation Research 46

      Pages: 205-214

    • Related Report
      2005 Annual Research Report
  • [Journal Article] DNA酸化への防御戦略-塩基除去修復を中心に2005

    • Author(s)
      張秋梅, 中村允耶, 米倉慎一郎, 米井脩治
    • Journal Title

      蛋白質・核酸・酵素 50

      Pages: 322-329

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 塩基除去修復の構成とヒトDNAグリコシラーゼの機構2005

    • Author(s)
      張 秋梅, 米倉慎一郎, 中村允耶, 金 貴花, 米井脩治
    • Journal Title

      放射線生物研究 40

      Pages: 185-201

    • Related Report
      2005 Annual Research Report
  • [Journal Article] DNA glycosylase activities for thymine residues oxidized in the methyl group are functions of the hNEIL1 and hNTH12005

    • Author(s)
      T.Doi, S.Yonekura, K.Tano, S, Yasuhira, S.Yonei, Q.-M.Zhang
    • Journal Title

      DNA Repair 4

      Pages: 71-79

    • Related Report
      2004 Annual Research Report
  • [Journal Article] DNA repair fidelity of base excision repair pathways in human cell extracts2005

    • Author(s)
      Q.-M.Zhang, G.L.Dianov
    • Journal Title

      DNA Repair 4

      Pages: 263-270

    • Related Report
      2004 Annual Research Report
  • [Journal Article] DNA酸化への防御戦略-塩基除去修復を中心に2005

    • Author(s)
      張秋梅, 中村允耶, 米倉慎一郎, 米井脩治
    • Journal Title

      蛋白質・核酸・酵素 50(印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Increased sensitivity to sparsely ionizing radiation due to excessive base excision in clustered DNA damage sites in Escherichia coli2005

    • Author(s)
      P.-W.Chang, Q.-M.Zhang, K.Takatori, A.Tachibana, S.Yonei
    • Journal Title

      International Journal of Radiation Biology 81(印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The Shizosaccharomyces pombe homolog (SpMYH) of the Escherichia coli MutY is required for removal of guanine from 8-oxoguanine/guanine mispairs to prevent G:C to C:G transversions2005

    • Author(s)
      T.Doi, S.Yonekura, K.Tano, S, Yasuhira, S.Yonei, Q.-M.Zhang
    • Journal Title

      Journal of Radiation Research 81(印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Recombinant Shizosaccharomyces pombe Nth1 protein exhibits DNA glycosylase activities for 8-oxo-7,8-dihydroguanine residues oxidized in the methyl group

    • Author(s)
      S.Yonekura, N.Nakamura, T.Doi, H.Sugiyama, S.Yonei, Q.-M.Zhang.
    • Journal Title

      International Journal of Radiation Biology (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Base excision repair fidelity in normal and cancer cells

    • Author(s)
      K.K.L.Chan, Q.-M.Zhang, G.L.Dianov
    • Journal Title

      Mutagenesis (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 電磁場生命科学(共著書)2005

    • Author(s)
      張秋梅, 米井脩治
    • Total Pages
      366
    • Publisher
      京都大学学術出版会
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 電磁場生命科学(宮越順二編)2005

    • Author(s)
      張 秋梅, 米井脩治
    • Total Pages
      396
    • Publisher
      京都大学出版会
    • Related Report
      2005 Annual Research Report

URL: 

Published: 2004-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi