哺乳動物細胞有一套核酸切除修復機制(nucleotide excision repair；NER)負責修復由短波長紫外線照射或特定化學物所產生的DNA傷害。Xeroderma pigmentosum group D (XPD)蛋白，是一種5’ 往3’ 方向的DNA 解旋脢，與XPB等其他蛋白同為為轉錄因子TFIIH附合體中的其中一員，同時參與核酸切除修復與轉錄機制( transcription)。若XPD發生突變會導致兩種不同臨床症狀的罕見隱性遺傳性疾病，一為色素性乾皮症（xeroderma pigmentosum; XP）；另一種為髮硫發育障礙（trichothiodystrophy; TTD) 。這兩種病患對於光照非常敏感，此外XP 病人具有相當高的癌症罹患率。在這個研究中，我嘗試比較正常的人類纖維母細胞（MSU-1）與來自TTD 及XP病人分離出來的纖維母細胞（TTD10VI, R658H；XP22VI, R683W）研究其對於DNA傷害的反應。我發現XP22VI對紫外線最為敏感其次是TTD10VI；並嘗試找出這種不同程度的敏感度與修復能力、細胞凋亡及p53和XPB蛋白表現量的相關性。但是根據我的實驗數據顯示，紫外線敏感度和上述因子並沒有呈現絕對相關性。另外我發現這三株細胞對於過氧化氫的敏感度恰與紫外線相反。由於TTD10VI與XP22VI突變的位置不相同，因而推論轉錄功能影響程度不同而導致不同的紫外線敏感度。但是更確切的分子機制仍須仰賴後續進一步的研究。

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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