Role for p53 in the recovery of transcription and protection against apoptosis induced by ultraviolet light.
We have previously suggested that the inhibition of RNA polymerase II-mediated transcription after exposure to UV light promotes the accumulation of p53 and the induction of apoptosis (Oncogene 13, 823-831). However, it was not clear whether p53 induction was contributing to apoptosis. Here we report that apoptosis is triggered at lower UV doses in p53-deficient Li-Fraumeni syndrome (LFS) and human papillomavirus (HPV) E6 expressing fibroblasts than in normal cells, suggesting that p53 can be protective against UV-induced apoptosis. There is no significant difference in the effect of UV-irradiation on the cell cycle distribution of normal and primary LFS fibroblasts. Importantly, the recovery of nascent mRNA synthesis in all p53-deficient fibroblasts is significantly impaired compared with control cells after exposure to relevant doses of UV light. Taken together, our results suggest that wild-type p53 can protect cells against UV-induced apoptosis by facilitating the recovery of transcription. Furthermore, we suggest that the capacity of cells to recover transcription after genotoxic damage is an important determinant of sensitivity to apoptosis.
McKay
B C
BC
Department of Radiation Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor 48109-0936, USA. bcmckay@umich.edu
Ljungman
M
M
D017209:Apoptosis / Q000528:radiation effects*; D002478:Cells, Cultured; D004260:DNA Repair; D005347:Fibroblasts / Q000528:radiation effects; D016193:G1 Phase; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis; D012878:Skin Neoplasms / Q000209:etiology; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D014466:Ultraviolet Rays
D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53