A mouse model for the nucleotide excision repair disorder Cockayne syndrome (CS) was generated by mimicking a truncation in the CSB(ERCC6) gene of a CS-B patient. CSB-deficient mice exhibit all of the CS repair characteristics: ultraviolet (UV) sensitivity, inactivation of transcription-coupled repair, unaffected global genome repair, and inability to resume RNA synthesis after UV exposure. Other CS features thought to involve the functioning of basal transcription/repair factor TFIIH, such as growth failure and neurologic dysfunction, are present in mild form. In contrast to the human syndrome, CSB-deficient mice show increased susceptibility to skin cancer. Our results demonstrate that transcription-coupled repair of UV-induced cyclobutane pyrimidine dimers contributes to the prevention of carcinogenesis in mice. Further, they suggest that the lack of cancer predisposition in CS patients is attributable to a global genome repair process that in humans is more effective than in rodents.

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doi.org/10.1016/S0092-8674(00)80223-8, hdl.handle.net/1765/3116
Erasmus MC: University Medical Center Rotterdam

van der Horst, G., van Steeg, H., Berg, R., van Gool, A., de Wit, J., Weeda, G., … Hoeijmakers, J. (1997). Defective transcription-coupled repair in Cockayne syndrome B mice is associated with skin cancer predisposition. Cell, 89(3), 425–435. doi:10.1016/S0092-8674(00)80223-8