Mutagenic deamination of cytosine residues in DNA

Nature. 1980 Oct 9;287(5782):560-1. doi: 10.1038/287560a0.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cytidine Deaminase / metabolism
  • Cytosine Nucleotides / metabolism*
  • DNA Glycosylases*
  • DNA Repair
  • Escherichia coli
  • Methylation
  • Mutation*
  • N-Glycosyl Hydrolases / metabolism*
  • Structure-Activity Relationship
  • Uracil-DNA Glycosidase

Substances

  • Cytosine Nucleotides
  • DNA Glycosylases
  • N-Glycosyl Hydrolases
  • Uracil-DNA Glycosidase
  • Cytidine Deaminase