Nucleic Acids Research Advance Access originally published online on July 10, 2007
Nucleic Acids Research 2007 35(14):4833-4844; doi:10.1093/nar/gkm497
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Nucleic Acids Research, 2007, Vol. 35, No. 14 4833-4844
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Chemistry |
Quantification of oxidative single-base and intrastrand cross-link lesions in unmethylated and CpG-methylated DNA induced by Fenton-type reagents
Department of Chemistry-027, University of California, Riverside, CA 92521-0403,USA
*To whom correspondence should be addressed. Tel: +1 951 827 2700; Fax: +1 951 827 4713; Email: yinsheng.wang{at}ucr.edu.
Received May 5, 2007. Revised June 2, 2007. Accepted June 6, 2007.
Methylation of cytosine at CpG sites in mammalian cells plays an important role in the epigenetic regulation of gene expression. Here, we assessed the formation of single-nucleobase lesions and intrastrand cross-link lesions (i.e. G[8-5]C, C[5-8]G, mC[5m-8]G, and G[8-5m]mC, where ‘mC’ represents 5-methylcytosine) in unmethylated and the corresponding CpG-methylated synthetic double-stranded DNA upon treatment with Fenton-type reagents [i.e. H2O2, ascorbate together with Cu(II) or Fe(II)]. Our results showed that the yields of oxidative single-nucleobase lesions were considerably higher than those of the intrastrand cross-link lesions. Although no significant differences were found for the yields of single-base lesions induced from cytosine and mC, the G[8-5m]mC cross-link was induced 
10 times more efficiently than the G[8-5]C cross-link. In addition, the mC[5m-8]G was induced at a level that was 15 times less than G[8-5m]mC, whereas the corresponding C[5-8]G intrastrand cross-link lesion was not detectable. Moreover, Cu(II) is 10-fold as effective as Fe(II) in inducing oxidative DNA lesions. These results suggest that oxidative intrastrand cross-link lesions formed at methylated-CpG sites may account for the previously reported mCG
TT tandem double mutations induced by Fenton-type reagents.
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