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

被引:28
作者
Nishiwaki, Y
Kobayashi, N
Imoto, K
Iwamoto, T
Yamamoto, A
Katsumi, S
Shirai, T
Sugiura, S
Nakamura, Y
Sarasin, A
Miyagawa, S
Mori, T [1 ]
机构
[1] Nara Med Univ, Radioisotope Res Ctr, Nara 6348521, Japan
[2] Nara Med Univ, Dept Dermatol, Nara 6348521, Japan
[3] Nara Med Univ, Med Genet Res Ctr, Nara 6348521, Japan
[4] Nara Med Univ, Dept Psychiat, Nara 6348521, Japan
[5] Inst Gustave Roussy, Lab Genet Instabil & Canc, Villejuif, France
关键词
CPD; 6-4PP; TTD; xeroderma pigmentosum; XPB;
D O I
10.1046/j.0022-202X.2004.22226.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
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 XP-D and that the cancer-free phenotype in TTD is unrelated to a DNA repair defect.
引用
收藏
页码:526 / 532
页数:7
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