Oxidative DNA damage contributes to aging, cancer, and other degenerative diseases.  Guanine is particularly vulnerable to oxidation, creating guanine radicals which form irreversible crosslinks to proteins.  Here, we investigate whether guanine radical reactivity in DNA-crosslinking reactions for the oligonucleotide 5'-ATATGATATGGATATGATAT-3' depends on its base pairing partner.  Cytosine derivatives were placed across from guanines, and a mismatch was inserted across from the 5'-G of a GG doublet.  Gel shift assays indicated that mismatches decreased in crosslinking in the order: G:G > G:A > G:T ~ G:C ~ G:U, consistent with the formation of a lower oxidation potential sink.  With the cytosine derivatives, the 5-bromocytosine duplex reacted more efficiently than the 5-methylcytosine, consistent with the existence of a more reactive cation radical with the 5-bromocytosine duplex than with the 5-methylcytosine duplex.  These findings indicate the reactivity of guanine in oxidative DNA-protein crosslinking reactions depends on its base pairing partner.

Influence of base pairing partner on DNA-protein crosslinking via guanine oxidation: Effect of mismatches and cytosine modification

243rd National Meeting (2012)

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