UV-induced G:C → A:T transitions at the APRT locus of Chinese hamster ovary cells cluster at frequently damaged 5′-TCC-3′ sequences
Abstract
We have determined the relative frequency in vitro of UV-induced cyclobutane pyrimidine dimers (py <> py) and (6-4) pyrimidine pyrimidone photoproducts (py(6-4)pyo) at individual sites in selected regions of the Chinese hamster ovary (CHO) adenine phosphoribosyltransferase (aprt) gene, and compared this to the observed specificity of UV-induced mutations (Drobetsky et al., 1987, 1989). Our results indicate that G:C-->A:T transition "hotspots" (multiple occurrences) at the chromosomal CHO aprt locus, the majority of which occur at 5'TCC-3', are clearly targeted at sites associated with a relatively high yield of py <> py and/or py(6-4)pyo. We conclude that photoproduct frequency plays a major role in UV-induced transition mutagenesis at 5'-TCC-3' sites at an endogenous locus in a rodent cell line, and that both py(6-4)pyo and py <> py have premutagenic potential.
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TCC to T dominated the mutational spectra of single genes isolated from UV-irradiated cell cultures.
“In the mid-1990s, Drobetsky et al. (29) and Marionnet et al. (30) observed that TCC → T dominated the mutational spectra of single genes isolated from UV-irradiated cell cultures.”
From Evidence for recent, population-specific evolution of the human mutation rate (2015) · cites this paper as [29]
TCC motifs are not hotspots for UV lesion formation but are disproportionately likely to have lesions develop into mutations rather than undergo error-free repair.
“Drobetsky et al. (29) compared the incidence of UV lesions to the incidence of mutations in irradiated cells and found that TCC motifs were not hotspots for lesion formation but instead were disproportionately likely to have lesions develop into mutations rather than undergoing error-free repair.”
From Evidence for recent, population-specific evolution of the human mutation rate (2015) · cites this paper as [29]
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References 29 · Cited by 21
- Authors
- Drobetsky, E. A., & Sage, E.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Drobetsky, E.A.
- ORCID
- Drobetsky, E.A.
- Venue
- Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
- Publisher
- Elsevier BV
- Published
- 1993-10
- Volume
- 289
- Issue
- 2
- Pages
- 131-138
- ISSN
- 0027-5107 (ISSN-L)
- 1386-1964
- OpenAlex
- W2070617659
- Cited by
- 21
- References
- 29
- Citations by year
- 2022: 1 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 1
- FWCI
- 0.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Mutation research. Fundamental and molecular mechanisms of mutagenesis (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Natural Sciences and Engineering Research Council of Canada
- Ligue Contre le Cancer
- Association pour la Recherche sur le Cancer
- Centre National de la Recherche Scientifique
- 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 mutagenesis, G:C to A:T transitions, cyclobutane pyrimidine dimers, mutational hotspots, CHO cells
- MeSH terms
- Adenine Phosphoribosyltransferase, Animals, Base Sequence, Cricetulus, Cyclobutanes, DNA, DNA Damage, DNA Mutational Analysis, Cricetinae, Molecular Sequence Data, Photochemistry, Pyrimidine Dimers, Pyrimidinones, Ultraviolet Rays, Mutagenesis, Site-Directed, CHO Cells, Point Mutation
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