DEFECTIVE TRANSCRIPTION-COUPLED REPAIR IN COCKAYNE-SYNDROME-B MICE ISASSOCIATED WITH SKIN-CANCER PREDISPOSITION

A mouse model for the nucleotide excision repair disorder Cockayne syn drome (CS) was generated by mimicking a truncation in the CSB(ERCC6) g ene of a CS-B patient. CSB-deficient mice exhibit all of the CS repair characteristics: ultraviolet (UV) sensitivity, inactivation of transc ription-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 mil d form. In contrast to the human syndrome, CSB-deficient mice show inc reased susceptibility to skin cancer. Our results demonstrate that tra nscription-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 attr ibutable to a global genome repair process that in humans is more effe ctive than in rodents.