Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3578-82.

Oxidized, deaminated cytosines are a source of C --> T transitions in vivo.

Author information

1
Division of Toxicology and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Abstract

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.

PMID:
9520408
PMCID:
PMC19878
DOI:
10.1073/pnas.95.7.3578
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center