This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Evans, M. K. Articles by Bohr, V. A. Search for Related Content PubMed PubMed Citation Articles by Evans, M. K. Articles by Bohr, V. A.

DNA Strand Bias in the Repair of the p53 Gene in Normal Human and Xeroderma Pigmentosum Group C Fibroblasts

Laboratory of Molecular Genetics, National Institute on Aging, NIH, Baltimore, Maryland 21224 [M. K. E., B. G. T., V. A. B.]; and Laboratory of Human Carcinogenesis, Division of Cancer Etiology, National Cancer Institute, NIH, Bethesda, Maryland 20892 [C. C. H.]

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 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 blas 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.

Received 8/13/93. Accepted 10/ 5/93.

This article has been cited by other articles:

				J.-H. Yoon, C.-S. Lee, and G. P. Pfeifer Simulated sunlight and benzo[a]pyrene diol epoxide induced mutagenesis in the human p53 gene evaluated by the yeast functional assay: lack of correspondence to tumor mutation spectra Carcinogenesis, January 1, 2003; 24(1): 113 - 119. [Abstract] [Full Text] [PDF]

				T. Hashimoto, Y. Tokuchi, M. Hayashi, Y. Kobayashi, K. Nishida, S.-i. Hayashi, Y. Ishikawa, K. Nakagawa, J.-i. Hayashi, and E. Tsuchiya Different Subtypes of Human Lung Adenocarcinoma Caused by Different Etiological Factors : Evidence from p53 Mutational Spectra Am. J. Pathol., December 1, 2000; 157(6): 2133 - 2141. [Abstract] [Full Text] [PDF]

				M.A. Wani, Q.Z. Zhu, M. El-Mahdy, and A.A. Wani Influence of p53 tumor suppressor protein on bias of DNA repair and apoptotic response in human cells Carcinogenesis, May 1, 1999; 20(5): 765 - 772. [Abstract] [Full Text] [PDF]

				S. N. Rodin and A. S. Rodin Strand asymmetry of CpG transitions as indicator of G1 phase-dependent origin of multiple tumorigenic p53 mutations in stem cells PNAS, September 29, 1998; 95(20): 11927 - 11932. [Abstract] [Full Text] [PDF]

				S Tornaletti and G. Pfeifer Slow repair of pyrimidine dimers at p53 mutation hotspots in skin cancer Science, March 11, 1994; 263(5152): 1436 - 1438. [Abstract] [PDF]

				C. Harris p53: at the crossroads of molecular carcinogenesis and risk assessment Science, December 24, 1993; 262(5142): 1980 - 1981. [PDF]