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Studies on DNA-PK controlling cell functions (analysis of double-gene destruction with PARP)

Research Project

Project/Area Number 10680665
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

TERAODA Hirobumi  Tokyo Medical and Dental University Medical Research Institute Professor, 難治疾患研究所, 教授 (30019137)

Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Keywordsknock-out mouse / DNA-dependent protein kinase / poly(ADP-ribose) polymerase / DNA repair / Ku protein / apoptosis / DNA依存症プロテインキナーゼ / DNA代謝
Research Abstract

The purpose of this research is to verify the hypothesis that DNA-dependent protein kinase (DNA-PK) exquisitely controls cell functions and cell fate. DNA-PK gene is responsible for mouse SCID defective in DNA end-joining process in V(D)J recombination and DNA double-strand break repair. Since several characteristics of DNA-PK are similar to those of poly(ADP-ribose) polymerase (PARP), the research focused on the relationship between them and complementarity to each other. PARP was phosphorylated by DNA-PK concomitantly with decrease in poly(ADP-ribosyl) action activity. At least in vitro, PARP stimulated DNA-PK activity as a DNA-binding regulatory component instead of Ku protein. Preparation of recombinant PARP of wild-type and truncated forms with individual and combined domains is now in progress. Although DNA-PK is not essential for cell survival, DNA-PK would subtly regulated DNA metabolism, including DNA replication, transcription, repair and recombination, for maintaining healthy life. In PARP-knock out (KO) mice, no severe dysfunction was observed except for lowering capacity of DNA repair. In order to analyze functional complementarity of DNA-PK and PARP, we intended to prepare double-gene KO mice and embryonic fibroblasts lacking both parp and DNA-PK genes. By mating scid+/-・PARP+/- mice, 129 males and 89 females were born. At present, no double-gene KO mice were obtained in genetially analyzed 51 mice of female. From 13.5-day embryos, primary cultured cells of fibloblasts lacking both parp and DNA-PK genes were obtained, out of which cell lines of embryonic fibloblast will be expected.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Nagaki S. et al.: "Non-histone chromosomal proeins HMG1 and 2 enhance ligation reaction of DNA double-strand breaks"Biochem. Biophys. Res. Commun.. 246. 137-141 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yumoto Y. et al.: "High mobility group proteins 1and 2 can function as DNA-binding regulatory components for DNA-dependent protein kinase in vitro"J. Biochem.. 124. 519-527 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Morio T. et al.: "Ku in the cytoplasm associates with CD40 in human B cells and translocates into the nucleus following incubation with IL-4 -----"Immunity. 11. 339-348 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yanokura M. et al.: "Cell death and cell-cycle arrest induced by incorporation of [^3H]thymidine into human haemopoietic cell lines"Int. J. Rad. Biol.. 76. 295-303 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 寺岡弘文,渡邉文晶: "DNA依存性プロテインキナーゼ"生化学 (総説). 72. 26-37 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 寺岡弘文: "実験医学別冊Bio Science新用語ライブラリー 「細胞周期」"田矢洋一,野島博,花岡文雄/編、羊土社. 6 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakaki, S. et al.: "Non-histone chromosomal proteins HMG1 and 2 enhance ligation reaction of DNA double-strand breaks."Biochem. Biophys. Res. Commun.. 246. 137-141 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yumoto, Y. et al.: "High mobility group proteins 1 and 2 can function as DNA-binding regulatory components for DNA-dependent protein kinase in vitro."J. Biochem.. 124. 519-527 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Morio, T. et al.: "Ku in the cytoplasm associates with CD40 in human B cells and translocates into the nucleus following incubation with IL-4 and CD40 mAb."Immunity. 11. 339-348 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yanokura, M. et al.: "Cell death and cell-cycle arrest induced by incorporation of [3H]thymidine into human haemopoietic cell lines."Int. J. Rad. Biol.. 76. 295-303 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Teraoka, H. and Watanabe, F.: "DNA-dependent protein kinase (in Japanese)"Seikagaku (Review). 72. 36-37 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Teraoka, H.: "In Cell Cycle (in Japanese)"(ed. by Taya, Y., Nojima, H., and Hanaoka, F.), Yodosha, RNase H, p. 108-109 ; DNA ligase, p. 112-113 ; ATM/ATR, p. 138-139.. (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Morio,T.et al: "Ku in the cytoplasm associates with CD40 in human B cells and translocates into the nucleus following incubation with IL-4 and .."Immunity. 11. 339-348 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yanokura,M.et al: "Cell death and cell-cycle arrest induced by incorporation of [^3H] thymidine into human haemopoietic cell lines"Int.J.Rad.Biol.. 76. 295-303 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 寺岡弘文,渡邉文晶: "DNA依存性プロテインキナーゼ「総説」"生化学. 72. 26-37 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 寺岡 弘文: "Bio Science 新用語ライブラリー・細胞周期"田矢洋一,野島 博,花岡文雄/編,羊土社. 6 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nagaki,S.,et al.: "Non-histone chromosomal proteins HMG1 and 2 enhance ligation reaction of DNA double-strand breaks." Biochem.Biophys.Res.Commun.246. 137-141 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yumoto,S.,et al.: "High mobility group proteins 1 and 2 can function as DNA-binding regulatory components for DNa-dependent.." J.Biochem.124. 519-527 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Teraoka,H.,et al.: "Differences in DMSO-induced G1 arrest and in apoptosis between Raji and Akata Burkitt's lymphoma cells." Cell Struct.Funct.23. 94 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Teraoka,H.,et al.: "DNA-dependent protein kinase modulates trans-activation of E2F." Cancer Detect.Prevent.22. S-61 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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