Ford J M, Lommel L, Hanawalt P C
Department of Biological Sciences, Stanford University, California 94305-5020.
Mol Carcinog. 1994 Jun;10(2):105-9. doi: 10.1002/mc.2940100208.
Mutations in the p53 tumor suppressor gene have been found in most human tumors. Analyses of the spectrum of p53 mutations in certain tumor types have shown a bias for mutations originating from lesions presumed to be in the untranscribed strand of the gene. This implies strand specificity for the formation or repair of DNA damage. We measured the induction and repair of ultraviolet light-induced cyclobutane pyrimidine dimers (CPD) in each strand of the human p53 gene in a normal human lung fibroblast cell line using quantitative Southern hybridization. We found that the removal of CPD from the transcribed strand was more rapid than that from the untranscribed strand of this gene, although the frequency of CPD induction was similar in both strands. Preferential repair of the transcribed strand of the p53 gene may account for the mutational spectra of this gene in human tumors.
在大多数人类肿瘤中都发现了p53肿瘤抑制基因的突变。对某些肿瘤类型中p53突变谱的分析表明，突变倾向于源自假定位于该基因非转录链上的损伤。这意味着DNA损伤形成或修复具有链特异性。我们使用定量Southern杂交技术，在正常人肺成纤维细胞系中测量了人p53基因每条链上紫外线诱导的环丁烷嘧啶二聚体（CPD）的诱导和修复情况。我们发现，该基因转录链上CPD的去除速度比非转录链更快，尽管两条链上CPD的诱导频率相似。p53基因转录链的优先修复可能解释了该基因在人类肿瘤中的突变谱。
