High sensitivity of the ultraviolet-induced p53 response in ultraviolet-sensitive syndrome, a photosensitive disorder with a putative defect in deoxyribonucleic acid repair of actively transcribed genes.
Previously, we reported a new category of photosensitive disorder named ultraviolet-sensitive syndrome (UVs S) [T. Itoh, T. Fujiwara, T. Ono, M. Yamaizumi, UVs syndrome, a new general category of photosensitive disorder with defective DNA repair, is distinct from xeroderma pigmentosum variant and rodent complementation group 1, Am. J. Hum. Genet. 56 (1995) 1267-1276.]. Cells derived from these patients show impaired recovery of RNA synthesis (RRS) after UV-irradiation irrespective of having a normal level of unscheduled DNA synthesis (UDS). These characteristics are reminiscent of Cockayne syndrome (CS) cells. By comparing sensitivity of the UV-induced p53 response in cells with different types of defects in nucleotide excision repair, we hypothesized that the UV-induced p53 response is triggered by inhibition of RNA synthesis [M. Yamaizumi, T. Sugano, UV-induced nuclear accumulation of p53 is evoked through DNA damage of actively transcribed genes independent of the cell cycle, Oncogene 9 (1994) 2775-2784.]. To test this hypothesis, we determined sensitivity of the p53 response in UVs S cells by immunostaining, Western blotting, and FACScan analysis. Maximal nuclear accumulation of p53 in the UVs S cells was observed with a one-third UV dose required for that in normal cells, while almost identical p53 responses were observed in UVs S and normal cells following treatment with heat or alpha-amanitin. Recovery of RNA synthesis after a low dose of UV-irradiation was impaired in UVs S cells to the same extent as seen in CS cells. These results provide further evidence to support our previous hypothesis regarding the mechanism of the p53 response induced by DNA damage.
Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Japan.
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Ohta
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Nitta
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Yamaizumi
D000546:Amanitins / Q000494:pharmacology; D002453:Cell Cycle / Q000235:genetics; D003057:Cockayne Syndrome / Q000235:genetics; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects; D004260:DNA Repair / Q000235:genetics* / Q000528:radiation effects; D005347:Fibroblasts; D005434:Flow Cytometry; D006358:Hot Temperature; D006801:Humans; D007150:Immunohistochemistry; D009687:Nuclear Proteins / Q000032:analysis; D010787:Photosensitivity Disorders / Q000235:genetics*; D012313:RNA / Q000096:biosynthesis / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D000546:Amanitins; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D012313:RNA