Comparison of the Structural and Dynamic Effects of 5-Methylcytosine and 5-Chlorocytosine in a CpG Dinucleotide Sequence
2013
Inflammation-mediated reactive molecules can result in an array of oxidized and halogenated DNA-damage products, including 5-chlorocytosine (ClC). Previous studies have shown that ClC can mimic 5-methylcytosine (mC) and act as a fraudulent epigenetic signal, promoting the methylation of previously unmethylated DNA sequences. Although the 5-halouracils are good substrates for base-excision repair, no repair activity has yet been identified for ClC. Because of the apparent biochemical similarities of mC and ClC, we have investigated the effects of mC and ClC substitution on oligonucleotide structure and dynamics. In this study, we have constructed oligonucleotide duplexes containing C, ClC, and mC within a CpG dinucleotide. The thermal and thermodynamic stability of these duplexes were found to be experimentally indistinguishable. Crystallographic structures of duplex oligonucleotides containing mC or ClC were determined to 1.2 and 1.9 A resolution, respectively. Both duplexes are B-form and are superimposa...
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