p53-dependent DNA repair and apoptosis respond differently to high- and low-dose ultraviolet radiation.
p53 plays an essential part in the maintenance of the cellular genetic stability after a DNA-damaging event such as ultraviolet (UV) radiation. Following UV radiation, the amount of p53 protein is elevated. The increased p53 is believed to induce cell cycle arrest, promote nucleotide excision repair (NER) and apoptosis. To study if cells respond differently to high- and low-dose UV radiation, we examined the DNA repair efficiency and apoptosis rate of human and murine fibroblasts after UV radiation. Using a host cell reactivation assay, we found that NER was increased after low doses but not after high doses of UV radiation. In contrast, apoptosis occurred only after the cells received high doses (over 200 J/m2), but not low doses of UVB. The induction of both NER and apoptosis was observed only in p53+/+ murine fibroblasts, not in p53-/- cells, indicating that both stress response mechanisms are dependent on wild-type p53 function. UV radiation induced the expression of p53 protein in a dose-dependent manner up to 400 J/m2. In contrast, p21waf1/cip1 was induced only after low doses and bax only after high doses of UV radiation, supporting the roles of p21waf1/cip1 and bax in NER and apoptosis, respectively. Taken together, these results indicate that cellular stress response to UV radiation depends on UV dose, DNA repair after low doses and apoptosis after high doses, and that both mechanisms are dependent on wild-type p53 function.
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Department of Medicine, Vancouver Hospital and Health Sciences Centre, University of British Columbia, Canada. gangli@unixg.ubc.ca
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D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D018929:Cell Culture Techniques; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000528:radiation effects; D004247:DNA / Q000528:radiation effects*; D004260:DNA Repair / Q000235:genetics*; D004307:Dose-Response Relationship, Radiation; D004791:Enzyme Inhibitors / Q000528:radiation effects; D005347:Fibroblasts / Q000528:radiation effects; D016158:Genes, p53 / Q000502:physiology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000528:radiation effects; D019253:Proto-Oncogene Proteins c-bcl-2; D011829:Radiation Dosage; D016159:Tumor Suppressor Protein p53 / Q000528:radiation effects; D014466:Ultraviolet Rays; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C494827:Bax protein, mouse; C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D004247:DNA