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• W2103625519 startingPage "583" @default.
• W2103625519 abstract "The mechanisms by which the p53 response is triggered following exposure to DNA-damaging agents have not yet been clearly elucidated. We and others have previously suggested that blockage of RNA polymerase II may be the trigger for induction of the p53 response following exposure to ultraviolet light. Here we report on the correlation between inhibition of mRNA synthesis and the induction of p53, p21WAF1 and apoptosis in diploid human fibroblasts treated with either UV light, cisplatin or the RNA synthesis inhibitors actinomycin D, DRB, H7 and alpha-amanitin. Exposure to ionizing radiation or the proteasome inhibitor LLnL, however, induced p53 and p21WAF1 without affecting mRNA synthesis. Importantly, induction of p53 by the RNA synthesis or proteasome inhibitors did not correlate with the induction of DNA strand breaks. Furthermore, cisplatin-induced accumulation of active p53 in repair-deficient XP-A cells occurred despite the lack of DNA strand break induction. Our results suggest that the induction of the p53 response by certain toxic agents is not triggered by DNA strand breaks but rather, may be linked to inhibition of mRNA synthesis either directly by the poisoning of RNA polymerase II or indirectly by the induction of elongation-blocking DNA lesions." @default.
• W2103625519 created "2016-06-24" @default.
• W2103625519 creator A5013464158 @default.
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• W2103625519 creator A5052545112 @default.
• W2103625519 creator A5062852769 @default.
• W2103625519 date "1999-01-21" @default.
• W2103625519 modified "2023-10-17" @default.
• W2103625519 title "Inhibition of RNA polymerase II as a trigger for the p53 response" @default.
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• W2103625519 doi "https://doi.org/10.1038/sj.onc.1202356" @default.
• W2103625519 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9989808" @default.
• W2103625519 hasPublicationYear "1999" @default.
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