Author(s): Kreutzer DA, Essigmann JM, Kreutzer DA, Essigmann JM
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Abstract 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.
This article was published in Proc Natl Acad Sci U S A
and referenced in Journal of AIDS & Clinical Research