Preferential repair of ultraviolet light-induced DNA damage in the transcribed strand of the human p53 gene.
Mutations in the p53 tumor suppressor gene have been found in most human tumors. Analyses of the spectrum of p53 mutations in certain tumor types have shown a bias for mutations originating from lesions presumed to be in the untranscribed strand of the gene. This implies strand specificity for the formation or repair of DNA damage. We measured the induction and repair of ultraviolet light-induced cyclobutane pyrimidine dimers (CPD) in each strand of the human p53 gene in a normal human lung fibroblast cell line using quantitative Southern hybridization. We found that the removal of CPD from the transcribed strand was more rapid than that from the untranscribed strand of this gene, although the frequency of CPD induction was similar in both strands. Preferential repair of the transcribed strand of the p53 gene may account for the mutational spectra of this gene in human tumors.
Department of Biological Sciences, Stanford University, California 94305-5020.
J M
JM
Ford
L
L
Lommel
P C
PC
Hanawalt
D002478:Cells, Cultured; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D043224:Deoxyribonuclease (Pyrimidine Dimer); D015246:Deoxyribonuclease EcoRI / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000378:metabolism; D005347:Fibroblasts / Q000502:physiology / Q000528:radiation effects; D016158:Genes, p53 / Q000528:radiation effects*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000502:physiology / Q000528:radiation effects; D011740:Pyrimidine Dimers / Q000378:metabolism; D014158:Transcription, Genetic / Q000528:radiation effects*; D014466:Ultraviolet Rays / Q000009:adverse effects
D011740:Pyrimidine Dimers; D004706:Endodeoxyribonucleases; D015246:Deoxyribonuclease EcoRI; D043224:Deoxyribonuclease (Pyrimidine Dimer)