Mutagenic deamination of cytosine residues in DNA

BK Duncan, JH Miller - Nature, 1980 - nature.com
BK Duncan, JH Miller
Nature, 1980nature.com
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 …
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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