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Mutagenic deamination of cytosine residues in DNA

Abstract

Spontaneous deamination converts cytosine to uracil, which is excised from DNA by the enzyme uracil-DNA glycosylase, leading to error-free repair. 5-Methylcytosine residues are deaminated to thymine, which cannot be excised and repaired by this system. As a result, 5-methylcytosine residues are hotspots for spontaneous transitions, as demonstrated in the lacI gene of Escherichia coli. We show here that in bacteria which lack uracil-DNA glycosylase (Ung) and cannot excise uracil residues from DNA, the rate of spontaneous transition at cytosine residues is raised to the hotspot rate at 5-methylcytosine residues. These studies provide direct evidence that the deamination of cytosine is a significant source of spontaneous mutations.

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Duncan, B., Miller, J. Mutagenic deamination of cytosine residues in DNA. Nature 287, 560–561 (1980). https://doi.org/10.1038/287560a0

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