P53 plays a protective role against UV- and cisplatin-induced apoptosis intranscription-coupled repair proficient fibroblasts

We previously reported that transcription-coupled repair (TCR)-deficient hu man fibroblasts are extremely sensitive to UV-induced apoptosis and this se nsitivity correlated with the induction of the p53 tumour suppressor. Howev er, we have also found that p53 can be protective against UV-induced apopto sis. Thus, prior to this study, it was not clear whether the induction of p 53 in TCR-deficient fibroblasts contributed to their death. To address this issue, we have expressed human papillomavirus E6 (HPV-E6) in primary fibro blasts derived from patients affected with xeroderma pigmentosum (complemen tation groups A, B and C) and Cockayne syndrome (complementation group B). We found that TCR-deficient (XP-A, XP-B and CS-B) fibroblasts were more sen sitive than TCR-proficient cells (XP-C and normal) to both UV light and cis platin treatment and this increase in sensitivity was not p53 dependent. Im portantly, HPV-E6 expression increased the sensitivity of TCR-proficient no rmal and XP-C fibroblasts to UV- and cisplatin-induced apoptosis. This incr ease in sensitivity correlated with a decrease in the capacity of HPV-E6 ex pressing cells to recover mRNA synthesis following UV-irradiation. Therefor e, we propose that p53 protects against UV- and cisplatin-induced apoptosis in a TCR-dependent manner and that p53 does not contribute strongly to the induction of apoptosis. in TCR-deficient fibroblasts.