Abstract
Studies of DNA base sequence alterations have shown that for every agent the mutagenic process is specific with respect to the types of base changes induced and the location of the changes in the DNA. Analysis of the types of mutations produced by mutagenic agents can provide insight into the mechanism of mutation and can suggest which DNA lesions may be involved in the actual mutagenic event. We have developed a system for the analysis of chemically induced base sequence alterations in the cI repressor gene of bacteriophage lambda using DNA sequencing techniques. To illustrate the utility of this type of analysis, we present the results obtained with ultraviolet light (UV). Irradiation of target DNA with UV alone, or UV followed by photoreactivating light (which removes dimers), produces mostly transitions at pyrimidine-pyrimidine sites. Conversely, irradiation with 313 nm light plus acetophenone (which produces only thymine dimers) produces mostly transversions at low efficiency. This and other evidence suggests that the actual premutagenic UV lesion in E. coli may not be pyrimidine-pyrimidine dimers, but rather pyr(6-4)pyo photoproducts.
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- Benzer S. ON THE TOPOGRAPHY OF THE GENETIC FINE STRUCTURE. Proc Natl Acad Sci U S A. 1961 Mar;47(3):403–415. doi: 10.1073/pnas.47.3.403. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brash D. E., Haseltine W. A. UV-induced mutation hotspots occur at DNA damage hotspots. Nature. 1982 Jul 8;298(5870):189–192. doi: 10.1038/298189a0. [DOI] [PubMed] [Google Scholar]
- Calos M. P., Lebkowski J. S., Botchan M. R. High mutation frequency in DNA transfected into mammalian cells. Proc Natl Acad Sci U S A. 1983 May;80(10):3015–3019. doi: 10.1073/pnas.80.10.3015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Calos M. P., Miller J. H. Genetic and sequence analysis of frameshift mutations induced by ICR-191. J Mol Biol. 1981 Nov 25;153(1):39–64. doi: 10.1016/0022-2836(81)90525-8. [DOI] [PubMed] [Google Scholar]
- Coulondre C., Miller J. H. Genetic studies of the lac repressor. IV. Mutagenic specificity in the lacI gene of Escherichia coli. J Mol Biol. 1977 Dec 15;117(3):577–606. doi: 10.1016/0022-2836(77)90059-6. [DOI] [PubMed] [Google Scholar]
- Miller J. H., Coulondre C., Farabaugh P. J. Correlation of nonsense sites in the lacI gene with specific codons in the nucleotide sequence. Nature. 1978 Aug 24;274(5673):770–775. doi: 10.1038/274770a0. [DOI] [PubMed] [Google Scholar]
- Miller J. H. Mutational specificity in bacteria. Annu Rev Genet. 1983;17:215–238. doi: 10.1146/annurev.ge.17.120183.001243. [DOI] [PubMed] [Google Scholar]
- Razzaque A., Mizusawa H., Seidman M. M. Rearrangement and mutagenesis of a shuttle vector plasmid after passage in mammalian cells. Proc Natl Acad Sci U S A. 1983 May;80(10):3010–3014. doi: 10.1073/pnas.80.10.3010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Skopek T. R., Hutchinson F. DNA base sequence changes induced by bromouracil mutagenesis of lambda phage. J Mol Biol. 1982 Jul 25;159(1):19–33. doi: 10.1016/0022-2836(82)90029-8. [DOI] [PubMed] [Google Scholar]
- Skopek T. R., Hutchinson F. Frameshift mutagenesis of lambda prophage by 9-aminoacridine, proflavin and ICR-191. Mol Gen Genet. 1984;195(3):418–423. doi: 10.1007/BF00341442. [DOI] [PubMed] [Google Scholar]
- Tindall K. R., Stankowski L. F., Jr, Machanoff R., Hsie A. W. Detection of deletion mutations in pSV2gpt-transformed cells. Mol Cell Biol. 1984 Jul;4(7):1411–1415. doi: 10.1128/mcb.4.7.1411. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Todd P. A., Glickman B. W. Mutational specificity of UV light in Escherichia coli: indications for a role of DNA secondary structure. Proc Natl Acad Sci U S A. 1982 Jul;79(13):4123–4127. doi: 10.1073/pnas.79.13.4123. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Walker G. C. Mutagenesis and inducible responses to deoxyribonucleic acid damage in Escherichia coli. Microbiol Rev. 1984 Mar;48(1):60–93. doi: 10.1128/mr.48.1.60-93.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wood R. D., Skopek T. R., Hutchinson F. Changes in DNA base sequence induced by targeted mutagenesis of lambda phage by ultraviolet light. J Mol Biol. 1984 Mar 5;173(3):273–291. doi: 10.1016/0022-2836(84)90121-9. [DOI] [PubMed] [Google Scholar]