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2003 Fiscal Year Final Research Report Summary

Repair of oxidative DNA damage in Mammalian cells

Research Project

Project/Area Number 13480162
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 環境影響評価(含放射線生物学)
Research InstitutionTohoku University

Principal Investigator

YASUI Akira  Tohoku Univ., 1DAC, Dept.Mol.genetics, Prof, 加齢医学研究所, 教授 (60191110)

Co-Investigator(Kenkyū-buntansha) TAKAO Masashi  Tohoku Univ., 1DAC, Dept.Mol.genetics, Lecturer, 加齢医学研究所, 講師 (70216612)
Project Period (FY) 2001 – 2003
KeywordsDNA damage / DNA repair / base excision repair / oxidative DNA damage / glycosylase
Research Abstract

Endonuclease III, encoded by nth in Escherichia coli, removes thymine glycols, a toxic oxidative DNA lesion. To determine the biological significance of this repair in mammals, we established a mouse mutated in mNth1, a homologue of nth, by gene targeting. The homozygous mNth1 mutant mouse showed no detectable phenotypic abnormality so far analyzed. Embryonic cells with or without wild-type mNth1 showed no difference in sensitivity to menadione or hydrogen peroxide. Thymine glycols produced in the mutant mouse liver DNA by X-ray irradiation disappeared with time, though more slowly than in wild-type mouse. In extracts from mutant mouse liver, we found, instead of mNTH1 activity, at least two novel DNA glycosylase activities against thymine glycols. One activity is significantly higher in the mutant than in wild-type mouse in mitochondria, while the other is another nuclear glycosylase, for thymine glycols. These results underscore the importance of base excision repair of thymine glycols both in the nuclei and in the mitochondria in mammals.

  • Research Products

    (10 results)

All 2003 2002

All Journal Article (10 results)

  • [Journal Article] Spatial and temporal assembly2003

    • Author(s)
      岡野 他
    • Journal Title

      Mol.Cell biol. 23

      Pages: 3974-3981

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Spatial and temporal assembly of the proteins involved in repair of single-strand breaks in Human cells.2003

    • Author(s)
      Okano S, Lan L, Caldecot K, Mori T, Yasui A.
    • Journal Title

      Mol.Cell.Biol. 23

      Pages: 3974-3981

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A back-up glycosylase in Nth1-knockout mice2002

    • Author(s)
      高尾 他
    • Journal Title

      J.Biol.Cehm. 277

      Pages: 42205-42213

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Identification of 5-formyluracil DNA glycosylase2002

    • Author(s)
      高部 他
    • Journal Title

      Nucleic Acids Res 30

      Pages: 3454-3463

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A Novel nuclear and mitochondrial glycosylases2002

    • Author(s)
      高尾 他
    • Journal Title

      EMRO J 21

      Pages: 3486-3493

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Photorepair of RNA polymerase arrest2002

    • Author(s)
      Chigancas V 他
    • Journal Title

      Cell Becote Differ. 9

      Pages: 1099-1107

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A back-up glycosylase in Nth1-knockout mice is a functional Nei (endonuclease VIII) homologue.2002

    • Author(s)
      Takao M, Kanno S, Kobayashi K, Zhang Q-M, Yonei S, van der Horst G, Yasui A.
    • Journal Title

      J.Biol.Chem. 277

      Pages: 42205-42213

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Identification of 5-formyluracil DNA glycosylase activity of human hNTH1 protein.2002

    • Author(s)
      Miiyabe I., Zhang QM., Kino K., Sugiyama H., Takao M., Yasui A., Yonei S.
    • Journal Title

      Nucleic Acids Res. 30

      Pages: 3454-3463

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A Novel nuclear and mitochondrial glycosylases revealed by disruption of the mouse Nth1 gene encoding an endonuclease III : homologue for repair of thymine glycol.2002

    • Author(s)
      Takao M, Kanno S, Shiromoto T, Hasegawa R, Ide H, Iikeda S, Sarker AH, Seki S, Xing JZ, Le XC, Weinfeld M, Kobayashi K, Miyazaki J, Muijtjens M, Hoeijmakers JHJ, van der Horst G, Yasui.
    • Journal Title

      EMBO J. 21

      Pages: 3486-3493

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Photorepair of RNA polymerase arrest and apoptosis after ultraviolet irradiation in normal and XPB deficient rodent cells.2002

    • Author(s)
      Chigancas V, Batista LF, Brumatti G, Amarante-Mendes GP, Yasui A, Menck CF
    • Journal Title

      Cell Death Differ 9

      Pages: 1099-1107

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2006-07-11  

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