期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:1998
卷号:95
期号:7
页码:3578-3582
DOI:10.1073/pnas.95.7.3578
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要: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.