The specificity of UV-induced mutations at an endogenous locus in mammalian cells.
Open accessAbstract
We have used a rapid in vivo recombinational method to clone and completely sequence 34 UV-induced mutants at the adenine phosphoribosyltransferase (APRT) locus of Chinese hamster ovary cells. Among the mutants recovered, 26 were single base substitutions including 17 G.C----A.T transitions and a single A.T----G.C transition. Three of the 4 possible transversions accounted for the remaining 8 mutations. The G.C----T.A transversion was not recovered. Six tandem double or closely neighboring double-base substitutions, one double mutation consisting of a G.C----T.A transversion and an adjacent frameshift, as well as one single frameshift mutation were also recovered. UV-induced mutation appears to be targeted to dipyrimidine sites with only two exceptions. These include two double mutations where only one of the base substitutions occurred at a dipyrimidine site. The observed specificity of UV-light-induced mutations at the APRT locus is consistent with the argument that G.C----A.T transitions result primarily from the (6-4) pyrimidine pyrimidone lesion. A striking resemblance in the distribution of UV-induced mutants and a collection of 30 spontaneous mutants identified recently in our laboratory was noted. Both share a common strong site of multiple occurrence and a considerable degree of overlap with respect to site specificity. We speculate therefore that DNA context plays a significant role in mutation fixation in mammalian cells.
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- Authors
- Drobetsky, E. A., Grosovsky, A. J., & Glickman, B. W.
- Affiliations
- York University (CA)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1987-12
- Volume
- 84
- Issue
- 24
- Pages
- 9103-9107
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC299700
- OpenAlex
- W2020657751
- Cited by
- 211
- References
- 38
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2022: 3 · 2021: 19 · 2018: 1 · 2016: 1 · 2015: 2 · 2014: 7 · 2013: 2 · 2012: 2
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- UV-induced mutations, site specificity, adenine phosphoribosyltransferase, CHO cells, base substitutions, transversions, frameshift mutation, spontaneous mutation, mutation fixation
- MeSH terms
- Adenine Phosphoribosyltransferase, Animals, Base Sequence, Cell Line, Cell Survival, Cloning, Molecular, DNA Damage, Cricetinae, Mutation, Pentosyltransferases
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