Potential roles for p53 in nucleotide excision repair

Ultraviolet (UV) light-induced DIVA damage is repaired by the nucleotide ex cision repair pathway, which can be subdivided into transcription-coupled r epair (TCR) and global genome repair (GGR), Treatment of cells with a primi ng dose of UV light appears to stimulate both GGR and TCR, suggesting that these processes are inducible. GGR appears to be disrupted in p53-deficient fibroblasts, whereas the effect of p53 disruption on TCR remains somewhat controversial. Normal recovery of mRNA synthesis following UV irradiation i s thought to depend on TCR, We have found that the recovery of mRNA synthes is following exposure to UV light is severely attenuated in p53-deficient h uman fibroblasts. Therefore, p53 disruption may lead to a defect in TCR or a post-repair process required for the recovery of mRNA synthesis. Several different functions of p53 have been proposed which could contribute to the se cellular processes. We suggest that p53 could participate in GGR and the recovery of mRNA synthesis following UV exposure through the regulation of steady-state levels of one or more p53-regulated gene products important f or these processes. Furthermore, we suggest that the role of p53 in the rec overy of mRNA synthesis is important for resistance to UV-induced apoptosis .