HUMAN FIBROBLASTS EXPRESSING THE HUMAN-PAPILLOMAVIRUS E6 GENE ARE DEFICIENT IN GLOBAL GENOMIC NUCLEOTIDE EXCISION-REPAIR AND SENSITIVE TO ULTRAVIOLET-IRRADIATION

We investigated the role of wild-type p53 activity in modulating nucle otide excision repair after UV irradiation in normal and p53-deficient primary human fibroblasts created by expression of the human papillom avirus 16 E6 gene, Compared with parental cells, the E6-expressing fib roblasts were deficient in global genomic repair of both UV-induced cy clobutane pyrimidine dimers and 6-4 photoproducts but exhibited normal transcription-coupled repair. The E6-expressing cells were also more sensitive than their parental counterparts to UV irradiation and displ ayed similar levels of UV-induced apoptosis, These results suggest tha t disruption of wild-type p53 function by E6 expression results in sel ective loss of p53-dependent global genomic nucleotide excision repair , but not UV-induced apoptosis, leading to enhanced UV sensitivity.