%0 Journal Article
%T Mutagenic and Cytotoxic Properties of Oxidation Products of 5-Methylcytosine Revealed by Next-Generation Sequencing
%A Xi-Wen Xing
%A Yu-Li Liu
%A Mario Vargas
%A Yinsheng Wang
%A Yu-Qi Feng
%A Xiang Zhou
%A Bi-Feng Yuan
%J PLOS ONE
%D 2013
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0072993
%X 5-methylcytosine (5-mC) can be sequentially oxidized to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-foC), and finally to 5-carboxylcytosine (5-caC), which is thought to function in active DNA cytosine demethylation in mammals. Although the roles of 5-mC in epigenetic regulation of gene expression are well established, the effects of 5-hmC, 5-foC and 5-caC on DNA replication remain unclear. Here we report a systematic study on how these cytosine derivatives (5-hmC, 5-foC and 5-caC) perturb the efficiency and accuracy of DNA replication using shuttle vector technology in conjugation with next-g sequencing. Our results demonstrated that, in Escherichia coli cells, all the cytosine derivatives could induce CT transition mutation at frequencies of 0.17%¨C1.12%, though no effect on replication efficiency was observed. These findings provide an important new insight on the potential mutagenic properties of cytosine derivatives occurring as the intermediates of DNA demethylation.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0072993