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Title: Transcription-coupled repair: impact on UV-induced mutagenesis in cultured rodent cells and mouse skin tumors. Author: van Zeeland AA, Vreeswijk MP, de Gruijl FR, van Kranen HJ, Vrieling H, Mullenders LF. Journal: Mutat Res; 2005 Sep 04; 577(1-2):170-8. PubMed ID: 15949822. Abstract: UV-induced cyclobutane pyrimidine dimers (CPDs) are removed with accelerated speed from the transcribed strand of expressed genes in cultured mammalian cells by a process called transcription-coupled repair (TCR). It has been previously shown that this phenomenon has consequences for the molecular nature of the mutations induced by UV-light. Here, we review these data and show that TCR has not only a clear impact on UV-induced mutations in cultured mammalian cells but also on genes involved in tumor formation in the skin of UV-exposed mice. Mutations observed in the p53 gene in UV-induced squamous cell carcinoma are predominantly found at sites of dipyrimidines in the non-transcribed strand. In contrast, in UVC-irradiated Csb(-/-) Chinese hamster cells and in UVB-induced tumors in the Csb(-/-) mouse, almost all mutations are at positions of dipyrimidine sites in the transcribed strand of the mutated gene. Csb(-/-) mice appear to be susceptible to UVB-induced skin cancer in contrast to the human CSB patients. We speculate that the UVB-induced cancer susceptibility of Csb(-/-) mice is related to the absence of TCR as well as to a lack of a compensating global genome repair system for CPDs in mice.[Abstract] [Full Text] [Related] [New Search]