2003 Fiscal Year Final Research Report Summary
Trichothiodystrophy fibroblasts are deficient in the repair of ultraviolet-induced cyclobutane pyrimidine dimers and (6-4) photoproducts
Project/Area Number |
14570819
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Dermatology
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Research Institution | Nara Medical University |
Principal Investigator |
MIYAGAWA Sachiko Nara Medical University, Medicine, Professor, 医学部, 教授 (30094626)
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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)
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Project Period (FY) |
2002 – 2003
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Keywords | Trichothiodystrophy / Ultraviolet light / DNA damage / DNA repair / TFIIH / XPD / Nucleotide excision repair / Photocarcinogenesis |
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.
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Research Products
(6 results)