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 exhibitd 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.
Footnotes
-
↵1 This work was supported by Clinical Investigator Award K08-CA64330 from the National Cancer Institute (to J. M. F.), a Howard Hughes Undergraduate Research Fellowship (to E. L. B.), and Outstanding Investigator Grant CA44349 from the National Cancer Institute (to P. C. H.).
-
↵2 To whom requests for reprints should be addressed. Phone: (650) 723-2425; Fax: (650) 725-1848; E-mail: jmf@leland.stanford.edu.
- Received October 24, 1997.
- Accepted January 5, 1998.
- ©1998 American Association for Cancer Research.
Volume 58, Issue 4
