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Role of PCNA in Repair of Radiation-induced DNA Damage

Research Project

Project/Area Number 07457446
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 病態科学系歯学(含放射線系歯学)
Research InstitutionTokyo Medical and Dental University

Principal Investigator

SASAKI Takehito  Tokyo Medical and Dental Univ., Faculty of Dent., Prof., 歯学部, 教授 (90013896)

Co-Investigator(Kenkyū-buntansha) MIURA Masahiko  Tokyo Medical and Dental Univ., Faculty of Dent., Instructor, 歯学部, 助手 (10272600)
DOMON Masaharu  Tokyo Medical and Dental Univ., Faculty of Dent., Ass.Prof., 歯学部, 助教授 (60014198)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1995: ¥3,400,000 (Direct Cost: ¥3,400,000)
KeywordsPCNA / DNA Repair / DNA Polymerase / Excision Repair / Radiation / UV / 紫外線 / DNA修復 / 除去修復 / 放射線 / 突然変異 / ヌクレオチド
Research Abstract

The study supported by this grant has aleady been published as three papers in international journals as described elsewhere. The results are summarized as follows :
1. The ionizing-radiation induced PCNA-DNA complex formation was characterized in human diploid fibroblasts using an immunofluorescence method. It was revealed that complex formation is dependent on ATP and temperature, but not on protein synthesis or or activities of DNA polymerases delta/epsilon. The complex was lost 12-15 h after irradiation, which implies completion of the PCNA-dependent DNA synthesis, while it persisted when protein synthesis or activities of DNA polymerases delta epsilon were inhibited. Cells derived from a xeroderma pigmentosum group A patient, characteristic of complete deficiency in nucleotide excision repair (NER) , showed exactly the same time course as that in normal cells. These findings suggest that the repair of ionizing-radiation induced DNA damge requires newly synthesized proteins and DNA polymerases delta/epsilon activities to carry out DNA synthesis, and the initiation step is different from that in NER.
2. We pinpointed at which steps the PCNA complex is formed in NER employing XP-F and XP-G cells deficient in DNA endonucleases. Neither of cells showed PCNA complex formation, implicating that the complex is formed after coordinately regulated nicks at 3'and 5'sides of the DNA lesions in the NER process.
3. Mutational analysis of the XPA function on PCNA complex formation was performed using various mutations of XP-A cells. Mutations in the C4 type zinc finger domain completely lost the UV-induced complex formation, but those in the C2H2-like zinc finger domain did not affect the formation. These results were well correlated to the capacities of NER as reported previously. It was thus demonstrated that PCNA is closely linked the function of the XPA protein.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] M. Miura et al: "Characterizatin of X-Ray Induced Immunostaining of Proliferating Cell Nuclear Antigen in Human Diploid Fibroblsts." Radiation Research. 145. 75-80 (1996.)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M. Miura et al: "Roles of XPG and XPF/ERCC1 Endonucleases in UV-Induced Immunostaining of PCNA in Fibroblasts." Exptl Cell Res.226. 126-132 (1996.)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M. Miura et al: "Effect of XPA Gene Mutations on UV-Induced Immuostaining of PCNA in Fibroblasts fromxeroderma pigmentosum group A patients." Mutation Res. 364. 51-56 (1996.)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 佐々木 武仁: "頭頸部腫瘍の放射線抵抗性要因の分析" 頭頸部腫瘍. 21. 570-575 (1995.)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 佐々木 武仁: "多分割照射法の放射線生物学的背景" 頭頸部腫瘍. 22. 511-516 (1996.)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M. Miura and T. Sasaki: "Methods in Molecular Biology,DNA Repair Protocol:Eukaryotic Systems," Daryl S.Henderson,eds.Humana Press, (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 佐々木 武仁: 大川智彦 編、篠原出版、東京、,

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] "放射線治療と化学療法のの併用「癌放射線治療」" (1995.)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takehito Sasaki: "Analisis of factors influencing radioresistande of head and neck cancers" Head Neck Cancer. 21. 570-575 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Masahiko Miura, Shin Nakamura, Takehito Sasaki et al: "Roles of XPG and XPF/ERCC1 Endonucleases in UV-Induced Immunostaining of PCNA in Fibroblasts." Exptl.Cell Res. 226. 126-132 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Masahiko Miura and Takehito Sasaki: "Effect of XPA Gene Mutations on UV-Induced Immuostaining of PCNA in Fibroblasts from xeroderma pigmentosum group A patients." Mutat Res. 364. 51-56 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Masahiko Miura, Takehito Sasaki et al.: "Characterization of X-Ray-Induced Immunostaining of Proliferating Cell Nuclear Antigen in Human Diploid Fibroblsts." Radiat Res. 145. 75-80 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takehito Sasaki: "Radiobiological basis for altered fractionation radiotherapy and evaluation in mathematical model." Head Neck Cancer. 22. 511-516 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Nakamura et al: "Effect of the insulin-like growth factor l receptor on ionizing radiation-induced cell death in mouse embryo fibroblasts" Exptl Cell Res. 235(1). 287-294 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 佐々木武仁: "加速過分割照射法" 医学のあゆみ. 181(1). 713 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shimura M et al: "Characterization of room temperatue induced apoptosis in HL-60" FEBS Letters. 417. 379-384 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] M.Miura et al: "Methods in Molecular Biology,DNA Repair Protocol:Eukaryotic Systems" Daryl S.Henderson,eds.Humana Press, (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Masahiko Miura: "Roles of XPG and XPF/ERCC1 Endonucleases in UV-induced Immunostaining of PCNA in Fibroblasts" EXPERIMENTAL CELL RESEARCH. 226. 126-132 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Masahiko Miura: "Effect of XPA gene mutations on UV-induced immunostaining of PCNA in fibroblasts from xeroderma pigmentosum group A patients" Mutation Research. 364. 51-56 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 佐々木武仁: "多分割照射法の放射線生物学的背景" 頭頚部腫瘍. 22. 511-516 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 佐々木武仁: "肺癌に対する集学的治療は進歩したか" 渡辺洋宇他編 中山書店, 201 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Masahiko Miura: "Characterization of X-Ray-Induced Immunostaining of Proliferating Cell Nuclear Antigen in Human Diploid Fibroblasts" RADIATION RESEARCH. 145. 75-80 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Masahiko Miura: "Effect of a Mutation at Tyrosine 950 of the Insulin-like Growth Factor I Receptor on the Growth and Transformation of Cells^1" CANCER RESEARCH. 55. 663-667 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Masahiko Miura: "Different Effects on Mitogenesis and Transformation of a Mutation at Tyrosine 1251 of the Insulin-like Growth Factor I Receptor^*" JOURNAL OF BIOLOGICAL CHEMISTRY. 270. 22639-22644 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 佐々木 武仁: "頭頚部腫瘍の放射線抵抗性要因の分析" 頭頚部腫瘍. 21. 570-575 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 佐々木 武仁: "多分割照射法の進歩と今後の課題" 歯科放射線. 35. 113-115 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 佐々木 武仁: "癌放射線療法" 大川智彦 編 篠原出版, 939 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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