Cytosine oxidation products are mutagenic and may be important in epigenetic regulation of the genome. 5-hydroxy-2'-deoxycytidine (5-OH-dC) induces C to T transitions in E. coli at a rate of 2.5%. We show that the 5-OH-dC:dG base pair exhibits increased exchange of its imino proton with solvent. Base stacking is maintained throughout the duplex. The thermodynamic destabilization induced by 5-OH-dC could provide a thermodynamic mode of recognition by base excision repair enzymes. 5-hydroxymethyl-2'-deoxycytidine (5hmC) is an oxidation product of 5-methyl-dC (5mC) in the active demethylation of 5mC facilitated by the TET family of enzymes. However, thymine DNA glycosylase does not remove 5hmC. NMR reveals that base pairing is as stable as base pairs in the unmodified duplex. Base stacking is maintained throughout the duplex, which is confirmed by a 1 � resolution crystal structure. Supported by NIH grants R01 CA-29088 (B.G.) and R01 CA-55678 (M.P.S).

Structural and thermodynamic aspects of cytosine oxidation in DNA

244th National Meeting (2012)

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