Skin Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Skin Cancer, including details on identification, causes, prevention, treatment.

Transcription-coupled repair: impact on UV-induced mutagenesis in cultured rodent cells and mouse skin tumors.

van Zeeland AA, Vreeswijk MP, de Gruijl FR, van Kranen HJ, Vrieling H, Mullenders LF

Department of Toxicogenetics, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands.

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.

Published 5 September 2005 in Mutat Res, 577(1): 170-8.
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