Mutagenic deamination of cytosine residues in DNA.
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.
D003564:Cytidine Deaminase / Q000378:metabolism; D003597:Cytosine Nucleotides / Q000378:metabolism*; D045647:DNA Glycosylases; D004260:DNA Repair; D004926:Escherichia coli; D008745:Methylation; D009154:Mutation; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*; D013329:Structure-Activity Relationship; D051981:Uracil-DNA Glycosidase
D003597:Cytosine Nucleotides; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D051981:Uracil-DNA Glycosidase; D003564:Cytidine Deaminase