One-electron oxidation of DNA: the effect of replacement of cytosine with 5-methylcytosine on long-distance radical cation transport and reaction.
One-electron oxidation of duplex DNA generates a radical cation that migrates through the nucleobases until it is trapped by an irreversible reaction with water or oxygen. The trapping site is often a GG step, because this site has a relatively low ionization potential and this causes the radical cation to pause there momentarily. Modifications to guanine that lower its ionization potential convert it to a better trap for the radical cation. One such modification is the formation of the Watson-Crick base pair with cytosine, which is reported to very significantly decrease its ionization potential. Methylation of cytosine to form 5-methylcytosine (5-MeC) is a naturally occurring reaction in genomic DNA that may be associated with regions of enhanced oxidative damage. The G.5-MeC base pair is reported to be more rapidly oxidized than normal G.C base pairs. We examined the oxidation of DNA oligomers that were substituted in part with 5-MeC. Irradiation of a covalently linked anthraquinone group injects a radical cation into the DNA and results in strand cleavage after piperidine treatment. For the sequences examined, substitution of 5-MeC for C has no measurable effect on the reactions. Cytosine methylation is not a general cause of enhanced oxidative damage in DNA.
Kanvah
Sriram
S
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
Schuster
Gary B
GB
D044503:5-Methylcytosine / Q000737:chemistry*; D001345:Autoradiography; D001483:Base Sequence; D002412:Cations / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000737:chemistry*; D004579:Electron Transport; D008745:Methylation
D002412:Cations; D044503:5-Methylcytosine; D004247:DNA