| Summary: | 碩士 === 高雄醫學大學 === 醫學研究所 === 99 === Previously our studies showed that arecoline could inhibit DNA repair of UV-induced damages through, at least partly, repressing p53’s expression and transactivation activity. Since UV-induced damages are primarily repaired by the mechanism of nucleotide excision repair (NER), we hypothesized that arecoline might inhibit DNA repair via interfering with the machineries of NER. Among the factors involving in NER, DDB2 plays a role in recognition of DNA lesions. XPB and XPD contain helicase activity and can unwind the damaged double-strand DNA. To explore the molecular mechanism underlying arecoline-mediated inhibition of DNA repair, we examined the effect of arecoline on the promoter activity and expression of DDB2. The results showed that arecoline suppressed DDB2 promoter and mRNA expression. In contrast, the constitutive DDB2 protein level was increased by arecoline treatment, implying that arecoline might affect DDB2 protein stability or its degradation. The degradation of DDB2 is necessary for the downstream repair process of NER. Besides, co-immunoprecipitation and immunofluorescent assay showed that arecoline might affect the protein interaction of p53 and XPB or p53 and XPD. However, the consequences of these arecoline’s effects on NER wait for further investigation. Taken together, this study demonstrated that arecoline indeed could interfere with certain NER genes that might be critical for arecoline-mediated repression of NER.
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