Oxidized, Deaminated Cytosines are a Source of C → T Transitions in vivo

The most common base substitution arising from oxidative damage of DNA is a GC → AT transition. In an effort to determine the oxidized lesion(s) that gives rise to this mutation, the mutagenicity of three oxidized cytosines, 5-hydroxycytosine, 5-hydroxyuracil, and uracil glycol, were investigated in...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1998-03, Vol.95 (7), p.3578-3582
Main Authors: Kreutzer, Deborah A., Essigmann, John M.
Format: Article
Language:English
Subjects:
Bacteriophages
Biochemistry
Biological Sciences
Cytosine
DNA
DNA Damage
DNA Replication
DNA, Viral - genetics
DNA, Viral - metabolism
Enzymes
Escherichia coli
Genetic mutation
Genome, Viral
Genomes
Lesions
Mutagenesis
Mutation
Oligonucleotides
Oxidation
Oxidation-Reduction
Oxidative Stress - genetics
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Summary:The most common base substitution arising from oxidative damage of DNA is a GC → AT transition. In an effort to determine the oxidized lesion(s) that gives rise to this mutation, the mutagenicity of three oxidized cytosines, 5-hydroxycytosine, 5-hydroxyuracil, and uracil glycol, were investigated in Escherichia coli. An M13 viral genome was constructed to contain a single oxidized cytosine at a specific site. Replication in vivo of the single-stranded genomes yielded mutation frequencies of 0.05%, 83%, and 80% for 5-hydroxycytosine, 5-hydroxyuracil, and uracil glycol, respectively. The predominant mutation observed was C → T. A model for C → T oxidative mutagenesis is suggested in which initial cytosine oxidation is followed by deamination to a poorly repaired uracil derivative that is strongly miscoding during replication.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.95.7.3578