Defective transcription-coupled repair in Cockayne syndrome B mice is associated with skin cancer predisposition.
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.
|Keywords||0 (Repressor Proteins), 0 (Transcription Factors), 0 (Viral Proteins), 0 (phage repressor proteins), 148972-58-1 (ERCC6 protein), Alleles, Amino Acid Sequence, Animals, Cockayne Syndrome/*genetics/physiopathology, DNA Helicases/deficiency/genetics, DNA Repair/*physiology/radiation effects, Disease Models, Animal, EC 5.99.- (DNA Helicases), Female, Human, Male, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Mutagenesis/physiology, Photosensitivity Disorders/genetics/physiopathology, Repressor Proteins/genetics, Skin Neoplasms/*genetics/physiopathology, Support, Non-U.S. Gov't, Transcription Factors/genetics, Transcription, Genetic/*physiology/radiation effects, Ultraviolet Rays/adverse effects, Viral Proteins/genetics|
|Persistent URL||dx.doi.org/10.1016/S0092-8674(00)80223-8, hdl.handle.net/1765/3116|
van der Horst, G.T.J., van Steeg, H., Berg, R.J.W., van Gool, A.J., de Wit, J., Weeda, G., … Hoeijmakers, J.H.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