title: Human fibroblasts expressing the human papillomavirus E6 gene are deficient in global genomic nucleotide excision repair and sensitive to ultraviolet irradiation.
abstract: We investigated the role of wild-type p53 activity in modulating nucleotide excision repair after UV irradiation in normal and p53-deficient primary human fibroblasts created by expression of the human papillomavirus 16 E6 gene. Compared with parental cells, the E6-expressing fibroblasts were deficient in global genomic repair of both UV-induced cyclobutane 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 displayed similar levels of UV-induced apoptosis. These results suggest that disruption of wild-type p53 function by E6 expression results in selective loss of p53-dependent global genomic nucleotide excision repair, but not UV-induced apoptosis, leading to enhanced UV sensitivity.
authors.affiliation: Department of Biological Sciences, Stanford University, California 94305-5020, USA. jmf@leland.stanford.edu
authors.forename: J M
authors.initials: JM
authors.lastname: Ford
authors.forename: E L
authors.initials: EL
authors.lastname: Baron
authors.forename: P C
authors.initials: PC
authors.lastname: Hanawalt
mesh_terms: D017209:Apoptosis; D002453:Cell Cycle / Q000528:radiation effects; D002460:Cell Line; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D005347:Fibroblasts / Q000528:radiation effects* / Q000821:virology*; D005814:Genes, Viral; D016158:Genes, p53; D006801:Humans; D027383:Papillomaviridae / Q000235:genetics*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D013997:Time Factors; D014158:Transcription, Genetic; D014161:Transduction, Genetic; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C051550:E2 protein, Bovine papillomavirus; D014764:Viral Proteins; D013762:Tetrahydrofolate Dehydrogenase