• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Trichothiodystrophy fibroblasts are deficient in the repair of ultraviolet-induced cyclobutane pyrimidine dimers and (6-4) photoproducts

Research Project

Project/Area Number 14570819
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionNara Medical University

Principal Investigator

MIYAGAWA Sachiko  Nara Medical University, Medicine, Professor, 医学部, 教授 (30094626)

Co-Investigator(Kenkyū-buntansha) KOBAYASHI Nobuhiko  Nara Medical University, Medicine, Assistant Professor, 医学部, 講師 (70316074)
MORI Toshio  Nara Medical University, Medicine, Associate Professor, 医学部, 助教授 (10115280)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsTrichothiodystrophy / Ultraviolet light / DNA damage / DNA repair / TFIIH / XPD / Nucleotide excision repair / Photocarcinogenesis / ヌクレチオド除去修後 / 光線過敏症
Research Abstract

A photosensitive form of trichothiodystrophy (TTD) results from mutations in the same XPD gene as the DNA repair-deficient genetic disorder xeroderma pigmentosum group D (XP-D). Nevertheless, unlike XP, no increase in skin cancers appears in patients with TTD. Although the ability to repair ultraviolet (UV)-induced DNA damage has been examined to explain their cancer-free phenotype, the information accumulated to date is contradictory. In this study, we determined the repair kinetics of cyclobutane pyrimidine dimers (CPD) and (6-4)photoproducts (6-4PP) in three TTD cell strains using an enzyme-linked immunosorbent assay. We found that all three TTD cell strains are deficient in the repair of CPD and of 6-4PP. UV sensitivity correlated well with the severity of repair defects. Moreover, accumulation of repair proteins (XPB and proliferating cell nuclear antigen) at localized DNA damage sites, detected using micropore UV irradiation combined with fluorescent antibody labeling, reflected their DNA repair activity. Importantly, mutations of the XPD gene affected both the recruitment of the TFIIH complex to DNA damage sites and the TFIIH expression. Our results suggest that there is no major difference in the repair defect between TTD and XPD and that the cancer-free phenotype in TTD is unrelated to a DNA repair defect.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Toshio Mori: "Quantitation and visualization of ultraviolet-induced DNA damage using specific antibodies"J Nara Med Assoc. 53. 179-191 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kyoko Imoto: "The total amount of DNA damage determines ultraviolet-radiation-induced cytotoxicity after uniformor localized irradiation of human cells"J Invest Darmatol. 119. 1177-1182 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoko Nishiwaki: "Trichothiodystropy fibroblasts are deficient in the repair of UV-induced cyclobutane pyrimidine dimers and (6-4) photo products"J Invest Darmatol. 122(On line). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mori T: "Quantitation and visualization of ultraviolet-induced DNA damage using specific antibodies"J Nara Med Assoc. 53. 179-191 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Imoto K: "The total amount of DNA damage determines ultraviolet-radiation-induced cytotoxicity after uniform or localized irradiation of human cells"J Invest Dermatol. 119. 1177-1182 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nishiwaki Y: "Trichothiodystrophy fibroblasts are deficient in the repair of UV-induced cyclobutane pyrimidine dimers and (6-4) photoproducts"J Invest Dermatol. 112 (Feb 2^<nd> on line). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Toshio Mori: "Quantitation and visualization of ultraviolet-induced DNA damage using specific antibodies"J Nara Med Assoc. 53. 179-191 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kyoko Imoto: "The Total Amount of DNA Damage Determines Ultraviolet-radiation-induced Cytotoxicity After Uniform or Localized Irradiation of Human Cells"J Invest Dermatol. 119. 1177-1182 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoko Nishiwaki: "Trichothiodystrophy Fibroblasts Are Deficient in the Repair of Ultraviolet-Induced Cyclobutane Pyrimidine Dimers and (6-4)photoproducts"J Invest Dermatol. 122(on line). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Imoto K. et al.: "The Total Amount of DNA Damage Determines Ultraviolet-radiation-induced Cytotoxicity After Uniform or Localized Irradiation of Human Cells"J Invest. Dermatol.. 119. 1177-1182 (2002)

    • Related Report
      2002 Annual Research Report

URL: 

Published: 2002-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi