Defective Transcription-Coupled Repair in Cockayne Syndrome B Mice Is Associated with Skin Cancer Predisposition

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• 作者：Gijsbertus T. J. van der Horst ; Harry van Steeg ; Rob J. W. Berg ; Alain J. van Gool ; Jan de Wit ; Geert Weeda ; Hans Morreau ; Rudolf B. Beems ; Coen F. van Kreijl ; Frank R. de Gruijl ; Dirk Bootsma ; Jan H. J. Hoeijmakers
• 刊名：Cell
• 出版年：1997
• 出版时间：2 May 1997
• 年：1997
• 卷：89
• 期：3
• 页码：425-435
• 全文大小：2004 K

文摘

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.