Potential roles for p53 in nucleotide excision repair.
Ultraviolet (UV) light-induced DNA damage is repaired by the nucleotide excision repair pathway, which can be subdivided into transcription-coupled repair (TCR) and global genome repair (GGR). Treatment of cells with a priming 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 is thought to depend on TCR. We have found that the recovery of mRNA synthesis following exposure to UV light is severely attenuated in p53-deficient human 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 these 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 for these processes. Furthermore, we suggest that the role of p53 in the recovery of mRNA synthesis is important for resistance to UV-induced apoptosis.
McKay
B C
BC
Department of Radiation Oncology, Division of Cancer Biology, University of Michigan Comprehensive Cancer Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0936, USA. bcmckay@umich.edu
Ljungman
M
M
Rainbow
A J
AJ
D003057:Cockayne Syndrome / Q000235:genetics; D004247:DNA / Q000528:radiation effects*; D004260:DNA Repair / Q000235:genetics* / Q000528:radiation effects; D005347:Fibroblasts / Q000528:radiation effects; D017930:Genes, Reporter / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics*; D005822:Genetic Vectors / Q000008:administration & dosage; D006358:Hot Temperature; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000235:genetics* / Q000528:radiation effects; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics
D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D004247:DNA