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 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.