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遺伝情報維持の分子機構

Research Project

Project/Area Number 04354030
Research Category

Grant-in-Aid for Co-operative Research (B)

Allocation TypeSingle-year Grants
Research InstitutionOsaka University

Principal Investigator

田中 亀代次  大阪大学, 細胞生体工学センター, 教授 (80144450)

Co-Investigator(Kenkyū-buntansha) 花岡 文雄  理化学研究所, 細胞生理学研究室, 主任研究員 (50012670)
関 周司  岡山大学, 医学部, 教授 (50032884)
山泉 克  熊本大学, 医学部, 教授 (70107093)
内海 博司  京都大学, 原子炉尚実験所, 教授 (20025646)
安井 明  東北大学, 抗酸菌病研究所, 助手 (60191110)
Project Period (FY) 1992
Project Status Completed (Fiscal Year 1992)
KeywordsDNA修復 / 遺伝情報維持 / 色素性乾皮症 / 遺伝子発現制御 / 遺伝子ターゲッティング
Research Abstract

遺伝情報維持の分子機構を解明する目的で、以下の3つに分類される研究計画を立案し、研究打ち合わせ会議を開催し討議した。1)DNA修復遺伝子の単離、DNA修復蛋白の精製、inritroでの修復系の再構成等により、DNA修復酵素の構造と機能を解析する。2)遺伝情報維持の制御機構を解析する。3)DNA修復欠損あるいは亢進したマウスを作成し、遺伝情報維持機構の個体形成への役割について解析する。本年度の成果としては、色素性乾皮症(XP)A群蛋白が、柴外線照射による損傷をうけたDNAに特異性をもって結合すること、ヒトDNA除去修復遺伝子であるERCC5をクローニングし、それがXPG群の原因遺伝子であることを明らかにした。O^6メチルグアニンDNAメチルトランスフェラーゼのマウスおよびヒトゲノム遺伝子をクローニングし、純の構造を明らかにした。ショウバエからは、(6-4)光産物のみを認識する光回復酵素を精製し、脊椎物動(魚類)から始めて光回復酵素の遺伝子をクローニングした。SV4Oウイルスのミニ染色体に紫外線を照射したものを鋳型として、ヒト正常細胞の抽出液を用いた無細胞DNA修復系を確立した。全ての相補性群XP細胞はこの系で低いDNA修復合成活性しか示さなかった。マウスPCNAおよびDNAポリメラーゼβ遺伝子の転写制御に関わるシスエレメントを決定した。また、P53はPCNA遺伝子を抑制するが、DNAポリメラーゼβ遺伝子は抑制しないことも明らかにした。以上の成果により、高等真核生物のDNA修復機構の分子レベルでの解析が進展した。一方、遺伝子ターゲッティング法により、A群XP遺伝子を欠損したマウスを樹立した。このホモ接合体マウス由来の細胞は、A群XP細胞と同程度に紫外線に高感受性を示し、DNA除去修復能も欠損していた。このマウスはXPのモデルによる可能性が高く、DNA修復機構の個体形成への役割が解析できる。

Report

(1 results)
  • 1992 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Miyamoto I.: "Mutional analysis of structure and function of the xeroderma pigmentosum group A complementing protein." J.Biol.Chem.267. 12182-12187 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Eker APM.: "Xerodema pigmentosum group A correcting protein from calfhtymus." Mutat. Res.274. 211-224 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Sugimoto M.: "intrinsic radiosensitivity and PLD repair in osteosarcoma cell lines." Int.J.Radiat.Boil.62. 469-474 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Miyahara T.: "Enhancement of cytotoxiciy of cis-diaminedichloroplatium(II)by hyperthermia to Human esophageal cancer cells." Jap.J.Cancer Res.

    • Related Report
      1992 Annual Research Report
  • [Publications] Y.Wang: "Correlation between DNA methylation and expression of O^4-methylguanine-DNA methyltransferase gene in cultured human tumor cells." Mutat.Res.273. 221-230 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Ishizaki K.: "Repair of thymine dimers and(6-4)photoproducts in group A xeroderma pigmentosum cell lines harboring a transferred nomal chromosome 9." Photochem.Photobiol.56. 356-369 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yasui A.: "Mitochondrial DNA repair by photolyase." Mutat.Res.273. 231-236 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yasuhira S.: "Visible light-inducible photolyase geme from the goldfish Carassius auratus." J.Biol.Chem.267. 25644-25647 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yamaguchi M.: "Action of the mouse DNA polymerase β gene promoter by adenovirus type 12E1A proteins." Nucleic Acids Res.20. 2321-2325 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hirose F.,Yamaguchi M.,: "Novel 8-bp sequence(DRE)and specific binding factor(DREF)inovolved in the expression of Drosophila genes for DNA polymerase α and proliferationg cell nuclear antigen." J.Biol.Chem.

    • Related Report
      1992 Annual Research Report
  • [Publications] Yagi T.: "UV-induced base substiution mutations in a shuttle vector plasmid propagated in group C xeroderma pegmentosum cells." Mutat.Res.273. 213-220 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Moriwaki S.: "A case of xeroderma pigmentosum complementation group F with neurological abnormalities." British Jounal of Dermatology. 128. 91-94 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Sugasawa K.: "Cell-free repair of UV-damaged simian virus 40 chromosomes in human cell extracts. I.Development of a cell-free system detecting excision repair of UV-irradiated SV40 chromosomes." J.Biol.Chem.268. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Matsutani C.,Sugasawa K.,: "Cell-free repair of UV-damaged simian virus 40 chromosomes in human cell cxtracts.II.defective DNA repair synthesis by xerodema pigmentosum cell extracts." J.Biol.Chem.268. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Shiraishi A.: "Isolation and characterization of cDNA and genomic sequences for mouse O^6-methylguanine-DNA methyltransferase." Carcinogenesis. 13. 119-132 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Nakatsu Y.: "Organization and Expression of the Human Gene for O^6-methylguanine-DNA methyltransferase." Mutat.Res.293. 119-132 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Toda T.: "Indentification of cellular factors that recogneze UV-damaged DNA in drosophila milanogaster." Mutat.Res.273. 85-93 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Todo T.: "A new photoreactivating enzyme that specifically repairs ultraviolet light-induced(6-4)photoproducts." Nature. 361. 371-374 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Saijo M.: "Growth state and cell cycle dependentphosphorylation of DNA tpopispmerase II Swiss3T3 cells." Biochemistry. 33. 359-363 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yanagisawa J.: "Alteration of a DNA-dependemt ATPase activity in xeroderma pigmentosum complementation group C cells." J.Biol.Chem.267. 3585-3588 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yamamoto K.: "Characterization of the bacterially expessed Drosophila engrailed homeodomain." Journal of Biochem.111. 793-797 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Shirakawa M.: "Assignment of ^1, ^<15>N and ^<13>Cresonances,identification of elements of secondary stucture and determination of the global fold of thd DNA binding domain of GAl.4." Biochemistry.

    • Related Report
      1992 Annual Research Report
  • [Publications] Cheng K.C.: "8-hydroxyguanine,an abundant form of oxidative DNA damage,causes G→T and A→C substiutions." J.Biol.Chem.267. 166-172 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yamamoto F.: "Ubiquitous presence in mammalian cells of enzymatic activity specifically cleaving 8-hydroxyguanine-containing DNA." Jpn.J.Cancer Res.83. 351-357 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Strickland P.: "Further characteriztion of monoclonal antibody indicates specificity for(6-4)-dipyrimidine photoproducts." Photochem.Photobiol.55. 723-727 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Matsunaga T.: "Establishment and characterezation of a monoclona lantibody recognizing the Dewar ispmers of(6-4)photoproducts." Photochem.photobiol.

    • Related Report
      1992 Annual Research Report
  • [Publications] Yamanoto K.: "Dissection of functional domains in Escherichia in Escherichia coli DNA photolyase by likerinsertion muations." Mol.Gen.Genet.232. 1-6 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yamamoto K.: "Effect of flash photoreactivation on Escherechia coli recA enduction by ultraviolet light." FEMS Microbiol.letters. 90. 31-36 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Seki S.: "cDNA cloning,sequencing,expression and possible domain structure of human APEX nuclease homologous to Escherichea coli cxonuclease III." Biochim.Biophys.Acta. 1131(3). 287-299 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Seki S.: "A possible cause of heterogeneity of mammalian aqurinic/apyrimidinic endonuclease." Int.J.Biochem.25(1). 53-59 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Takahashi E.: "Precise localization of the excision repair gene,ERCC5,to human chromosome 13q32.3-q33.l by direct R-banding fluorescence en situ hybridization." Jap.Journal of Cancer Res.83. 1117-1119 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Tateishi S.: "Synthetic double-stranded DNA containing a pyrimidine dimer is encised at fourth phosphodiester linkage 3'to the pyrimidine dimer by human cell extract." Biochemistry.

    • Related Report
      1992 Annual Research Report
  • [Publications] Yamaizumi M.: "Protein factors involved in UV-enduced DNA lesions in human cells." Alfred Benzon Sym.35.

    • Related Report
      1992 Annual Research Report
  • [Publications] Gardner J.M.: "The mouse pink-eyed dilution gene:Association with human prader-Willi and Angelman Syndromes." Science. 257. 1121-1124 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Gondo Y.: "High-frequencey genetic reversion mediated by DNA duqlication:Mouse pink-eyed unstable mutation." Proc.Natl.Acad.Sci.USA. 90. 297-301 (1993)

    • Related Report
      1992 Annual Research Report

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Published: 1994-03-23   Modified: 2016-04-21  

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