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Molecular Mechanism for Maintainance of Genetic Information

Research Project

Project/Area Number 05270104
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionOsaka University

Principal Investigator

TANAKA Kiyoji  Institute for Molecular and Cellular Biology, Osaka University, Division of Cellular Genetics, Professor, 細胞生体工学センター, 教授 (80144450)

Co-Investigator(Kenkyū-buntansha) SEKIGUCHI Mutsuo  Fukuoka Dental College, Laboratory of Biology, Molecular Biology, professor, 生物学教室, 教授 (00037342)
YAMAIZUMI Masaru  Institute of Molecular Embryology and Genetics, Kumamoto University, Department, 医学部, 教授 (70107093)
YASUI Akira  Institute of Development, Aging and Cancer, Tohoku University, Department of Neu, 加齢医学研究所, 教授 (60191110)
UTSUMI Hiroshi  Research Reactor Institute, Kyoto University, Radiation Life Science, professor, 原子炉実験所, 教授 (20025646)
HANAOKA Fumio  Institute for Molecular and Cellular Biology, Osaka University, Division of Cell, 細胞生体工学センター, 教授 (50012670)
松原 謙一  大阪大学, 細胞生体工学センター, 教授 (20037394)
Project Period (FY) 1993 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥36,100,000 (Direct Cost: ¥36,100,000)
Fiscal Year 1996: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1995: ¥11,900,000 (Direct Cost: ¥11,900,000)
Fiscal Year 1994: ¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 1993: ¥11,200,000 (Direct Cost: ¥11,200,000)
KeywordsDNA repair / gene cloning / xeroderma pigmentosum / photolyases / X-ray crystallography / mismatch repair / gene targeting / knockout mice / p53蛋白質 / 発がん / 活性酸素 / 遺伝子ターゲッティング / モデルマウス / DNA結合
Research Abstract

The aim of this research is to analyze a molecular mechanism for maintainance of genetic information in higher eukaryotes including human and to analyze its role in embryogenesis, development, aging and carcinogenesis. Major achievements in this research are as follows. Group I : We cloned genes of photolyases for pyrimidine dimer and (6-4) photoproduct from prokaryotes, kangaroo rat, drosophila melanogaster, and goldfish. Human homologue of these photolyase genes has been cloned as well and functional analysis of the human homologue is in progress. We cloned the genes responsible for xeroderma pigmentosum groups A,C,and G,and analyzed their roles in the early steps of nucleotide excision repair and molecular basis of their deficiencies. Higher order structures of the three DNA repair proteins have been revealed by X-ray crystallography. Group II : We elucidated the control mechanisms of gene expression for PCNA and DNA polymerase beta. We cloned a mismatch repair gene MSH3 and found t … More hat the expression of the MSH3 gene was reduced in the leukemic cells which were RER positive. We found that the enzyme activity to repair 8-OH-Gua damage caused by the active oxygen was increased by the treatment with oxygen stress, smoking and aging. Group III : By the method of gene targeting in mouse ES cells, we established XPA-deficient or XPG-deficient mice, and O6-methylguanine-DNA-methyltransferase-deficient or 8-oxo-dGTPase-deficient mice. We also established RAD51-deficient mice which were lethal at the embryonal stage. The XPA-deficient mice were highly susceptible to UVB-induced skin carcinogenesis. Based on these results we concluded that we have accomplished the initial research projects such as molecular cloning of the important DNA repair genes, structural analysis of DNA repair proteins by X-ray crystallography and establishment of DNA repair gene-deficient mice by gene targeting. These achievements provide a basis for the breakthrough to unveiling the molecular mechanism for maintainance of genetic information. Less

Report

(5 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] Kuraoka,I.: "Identification of a damaged-DNA binding domain of the XPA protein." Mutat.Res.362. 87-95 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Miyauchi,H.: "Enhanced inflammation and immunosuppression by ultraviolet radiation in xeroderma pigmentosum group A(XPA)model mice." J.Invest.Dermat.107. 343-348 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Saijo,M.: "Sequential binding of DNA repair proteins RPA and ERCCl to XPA in vitro." Nucl.Acid.Res.24. 4719-4724 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sugasawa,K.: "HHR23B homolog,stimulates XPC protein in nucleotide excision repair in vitro." Mol.Cell.Biol.16. 4852-4861 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takao,M.: "Characterization of a UV endonuclease gene from the fission yeast Schizosaccharomyces pombe and its bacterial homolog." Nucleic Acid.Res.24. 1267-1271 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Itoh,T.: "Cockayne syndrome complementation group B associated with xeroderma pigmentosum phenotype." Hum.Genet.97. 176-179 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kuraoka, I.: "Identification of a damaged-DNA binding domain of the XPA protein." Mutat.Res.362. 87-95 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Miyauchi, H.: "Enhanced inflammation and immunosuppression by ultraviolet radiation in xeroderma pigmentosum group A (XPA) model mice." J.Invest.Dermat.107. 343-348 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Saijo, M.: "Sequential binding of DNA repair proteins RPA and ERCCl to XPA in vitro." Nucl.Acid.Res.24. 4719-4724 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sugasawa, K.: "HHR23B homolog, stimulates XPC protein in nucleotide excision repair in vitro." Mol.Cell.Biol.16. 4852-4861 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takao, M.: "Characterization of a UV endonuclease gene from the fission yeast Schizosaccharomyces pombe and its bacterial homolog." Nucleic Acid.Res.24. 1267-1271 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Itoh, T.: "Cockayne syndrome complementation group B associated with xeroderma pigmentosum phenotype." Hum.Genet.97. 176-179 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kuraoka,I.: "Identification of a damaged-DNA binding domain of the XPA protein." Mutat.Res.362. 87-95 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Miyauchi,H.: "Enhanced inflammation and immunosuppression by ultraviolet radiation in xeroderma pigmentosum group A(XPA)model mice." J.Invest.Dermat.107. 343-348 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Saijo.M.: "Sequential binding of DNA repair proteins RPA and ERCCl to XPA in vitro." Nucl.Acid.Res.24. 4719-4724 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sugasawa,K.: "HHR23B homolog,stimulates XPC protein in nucleotide excision repair in vitro." Mol.Cell.Biol.16. 4852-4861 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Takao,M.: "Characterization of a UV endonuclease gene from the fission yeast Schizosaccharomyces pombe and its bacterial homolog." Nucleic Acid.Res.24. 1267-1271 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Itoh,T.: "Cockayne syndrome complementation group B associated with xeroderma pigmentosum phenotype." Hum.Genet.97. 176-179 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakane,H.: "High incidence of UVB-or chemical carcinogen-induced skin tumours in mice lacking the xeroderma pigmentosum group A gene" Nature. 377. 165-168 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Matsuda,T.: "DNA repair protein XPA binds replication protein A" J.Biological Chemistry. 270. 4152-4157 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yajima,H.: "A eukaryotic gene encoding an endonuclease that specifically repairs DNA damaged by ultraviolet light" EMBO J.14. 2393-2399 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Shimamoto,T.: "Expression and functional analyses of Dxpa gene, the Drosophila homolog of a human excision repair gene XPA" J.Biological Chemistry. 270. 22452-22459 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kamiya,H.: "8-hydroxyadenine induces misincorporation in in vitro DNA Synthesis and mutations in NIH 3T3 cells" Nucleic Acid Research. 23. 2893-2899 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Cai,J-P.: "cDNA and gemomic sequences for rat 8-oxo-dGTPase that prevents occurrence of spontaneous mutations due to oxidation of guanine nuclootides" Carcinogenesis. 16. 2343-2350 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kiyoji Tanaka et al.: "DNA repair protein XPA binds replication protein A(RPA)." J.Biol.Chem.270. 4152-4157 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kiyoji Tanaka et al.: "The XPA protein is a zine metalloprotein with an ability to recognize various kinds of DNA damage." Mutation Research. 315. 229-237 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Akira Yasui et al.: "A new class of DNA photolyases present in various organisms includung aplacetal mammal." EMBO J.13. 6143-6151 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Fumio Hanaoka et al.: "Purification and cloning of a nucleotide excision repair complex involving the xerodema pigmentosum group C protein and a human homologue of yeast RAD 23." EMBO J.13. 1834-1843 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Masaru Yamaizumi et al.: "UV-induced nuclear accumulation of p53 is evoked through DNA damage of actively transcribed genes independent of the cell cycle." Oncogene. 9. 2775-2784 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Mutsuo Sekiguchi et al.: "Genomic structure and chromosome location of the human mutT homolog gene hMTH1 encoding 8-oxo-dGTPase for prevention of A:t to C:G transversion." Genomics. 24. 485-490 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Satokata,I.et al.: "Genomic characterization of the human DNA excision repair-controlling gene XPA." Gene. 136. 345-348 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Utsumi,H.et al.: "Human melanoma cells:the relationship between their radiosensitivity and the repair of potentially lethal damage." Radiat.Oncol.Invest.1. 129-133 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] van Vuuren,A.J.et al.: "Evidence for a repair enzyme complex involving ERCC1 and complementing activities of ERCC4,ERCC11 and xeroderma pigmentosum group F." EMBO J.12. 3693-3701 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tateishi,S.et al.: "Human nucleotide excision nuclease inciscs synthetic double-standed DNA containing a pyrimidine dimer at the fourth phosphodiester linkage 3' to the pyrimidine dimer." Biochemistry. 32. 1541-1547 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sakumi,K.et al.: "Cloning and expression of cDNA for a human enzyme that hydrolyzes 8-oxo-dGTP,a mutagenic substrate for DNA synthesis." J.Biol.Cem.268. 23524-23530 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sato,M.et al.: "Ultraviolet-specific mutations in p53 gene in skin tumors in xeroderma pigmentosum patients." Cancer Res.53. 2944-2946 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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