title: DNA strand bias in the repair of the p53 gene in normal human and xeroderma pigmentosum group C fibroblasts.
abstract: We have measured the gene-specific and strand-specific DNA repair of UV-induced cyclobutane pyrimidine dimers in the p53 tumor suppressor gene in a normal, repair-proficient human fibroblast strain and in fibroblasts from a patient with the repair deficient disorder xeroderma pigmentosum, complementation xeroderma pigmentosum group C (XP-C). In both cell strains, repair was measured in the p53 gene and in its individual DNA strands. For comparison, the repair also was measured in other genomic regions in these human fibroblast strains, including the housekeeping gene dihydrofolate reductase, and two inactive genomic regions, the delta globin gene, and the 754 locus of the X chromosome. In both cell strains, we find that the p53 gene is repaired faster than the dihydrofolate reductase gene and much more efficiently than the inactive genomic regions. Selective repair of the transcribed DNA strand of p53 is observed in both human cell strains; the strand bias of repair is particularly distinct in XP-C. Mutations specific to the nontranscribed strand may occur due to replication errors at the sites of unrepaired DNA damage. Therefore, our results predict that the majority of mutations in skin cancers, especially those from patients with XP-C, would occur on the nontranscribed strand of the p53 gene. Indeed, Dumasz et al. (Proc. Natl. Acad. Sci. USA, in press, 1993) report such a strand bias of p53 mutation in skin cancers from XP-C patients.
authors.affiliation: Laboratory of Molecular Genetics, National Institute on Aging, NIH, Baltimore, Maryland 21224.
authors.forename: M K
authors.initials: MK
authors.lastname: Evans
authors.forename: B G
authors.initials: BG
authors.lastname: Taffe
authors.forename: C C
authors.initials: CC
authors.lastname: Harris
authors.forename: V A
authors.initials: VA
authors.lastname: Bohr
mesh_terms: D004247:DNA / Q000528:radiation effects; D004260:DNA Repair; D005347:Fibroblasts; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics*
chemical_list: D004247:DNA; D013762:Tetrahydrofolate Dehydrogenase