p53 responsive nucleotide excision repair gene products p48 and XPC, but not p53, localize to sites of UV-irradiation-induced DNA damage, in vivo.
The p53 tumor suppressor gene is an important mediator of the cellular response to ultraviolet (UV)-irradiation-induced DNA damage and affects the efficiency of the nucleotide excision repair (NER) pathway. The mechanism by which p53 regulates NER may be through its ability to act as a transcription factor, and/or through direct interactions with damaged DNA or the repair machinery. p53 has been shown to regulate the expression of the DDB2 gene (encoding the p48 protein) and the XPC gene, two important components of the NER pathway involved in DNA damage recognition. In this study, a localized UV-irradiation technique was used to examine the localization of p53, p48 and XPC proteins in relation to sites of UV photoproducts, in vivo. We did not observe any specific co-localization of p53 with sites of UV-induced DNA damage, but did observe rapid co-localization of both p48 and XPC to these sites. p48 bound to UV photoproducts in cells mutant or deficient for either p53, XPC or XPA, and p48 enhanced XPC binding to lesions, suggesting that p48 is a very early recognition factor of DNA damage. We propose that p53 functions to transcriptionally regulate the DDB2 and XPC NER genes, but does not activate the NER pathway through direct interactions with UV-induced damaged DNA or other repair factors.
Fitch
Maureen E
ME
Department of Medicine, Division of Oncology, 1115 CCSR Bldg, 269 Campus Drive, Stanford University Medical School, CA 94305-5151, USA.
Cross
Irina V
IV
Ford
James M
JM
D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D005786:Gene Expression Regulation; D016158:Genes, p53 / Q000502:physiology; D006801:Humans; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000378:metabolism
C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; C086984:XPC protein, human; D004247:DNA