| Summary: | 碩士 === 國立清華大學 === 分子醫學研究所 === 94 === Mammalian cellular genomic DNA damages caused by UV irradiation of short-wavelength or by many chemicals rely on the mechanism of nucleotide excision repair (NER) to recover from the lesions. The xeroderma pigmentosum group D (XPD) is one of the NER components. XPD functions as a helicase in association with another helicase XPB and others in TFIIH complex, which is also involved in gene transcription. Defects in XPD can be associated with two different rare hereditary disorders: xeroderma pigmentosum (XP) and trichothiodystrophy (TTD). Both XP and TTD patients are, in general, hypersensitive to exposure of sun light, only XP patients have high risk of cancer. In this study, the UV sensitivity among the NER proficient (MSU-1) and deficient cell lines (TTD10VI and XP22VI) were re-examined. The UV sensitivity of the three cell lines varied significantly and was in the order of XP22VI, TTD10VI and MSU-1. I tried to correlate the differential UV sensitivities of the cells to parameters of each individual cell lines including the excision rate of UV-induced DNA adducts, UV-induced apoptosis, the p53 and XPB protein levels. The correlation was only partial; none of the parameters was correlated successfully with the UV sensitivity. Interestingly, the sensitivity to hydrogen peroxide of these cell lines was in reverse order of that of UV sensitivity. Since TTD10VI and XP22VI are XPD homozygous with XPD defect at different positions, which may have different effect on transcription, it is suspected that the transcription may be involved in the differential UV sensitivity in XP and TTD cells.
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