Defective transcription-coupled repair in Cockayne syndrome B mice is associated with skin cancer predisposition

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

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283 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)425-435
Aantal pagina's11
TijdschriftCell
Volume89
Nummer van het tijdschrift3
DOI's
StatusGepubliceerd - 2 mei 1997
Extern gepubliceerdJa

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