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 ult raviolet-sensitive syndrome (UVs S) [T. Itoh, T. Fujiwara, T. One, hi. Yama izumi, UVs syndrome, a new general category of photosensitive disorder with defective DNA repair, is distinct from xeroderma pigmentosum variant and r odent complementation group 1, Am. J. Hum. Genet. 56 (1995) 1267-1276.]. Ce lls derived from these patients show impaired recovery of RNA synthesis (RR S) after UV-irradiation irrespective of having a normal level of unschedule d DNA synthesis (UDS). These characteristics are reminiscent of Cockayne sy ndrome (CS) cells. By comparing sensitivity of the W-induced p53 response i n cells with different types of defects in nucleotide excision repair, we h ypothesized that the UV-induced p53 response is triggered by inhibition of RNA synthesis [hl. 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 immunostai ning, Western blotting, and FACScan analysis. Maximal nuclear accumulation of p53 in the UVs S cells was observed with a one-third UV dose required fo r that in normal cells, while almost identical p53 responses were observed in WS S and normal cells following treatment with heat or alpha-amanitin. R ecovery of RNA synthesis after a low dose of W-irradiation was impaired in UVs S cells to the same extent as seen in CS cells. These results provide f urther evidence to support our previous hypothesis regarding the mechanism of the p53 response induced by DNA damage. (C) 1999 Elsevier Science B.V. A ll rights reserved.