Stability, miscoding potential, and repair of 2'-deoxyxanthosine in DNA: implications for nitric oxide-induced mutagenesis.

Nitric oxide (NO(*)) reacts with guanine in DNA and RNA to produce xanthine (X) as a major product. Despite its potential importance in NO(*)-mediated mutagenesis, the biochemical properties of X in polynucleotides have been relatively unexplored. We describe the synthesis and chemical characterization of xanthine-containing oligonucleotides and report on the susceptibility of X to depurination, its miscoding potential during replication by polymerases, and its recognition and excision by several members of the base excision repair (BER) family of DNA glycosylases. At neutral pH, X was found to be only slightly less stable than guanine to depurination (k(X)/k(G) = 1.19), whereas at pH Mpg > Nth > Fpg. Implications of these results for the induction of mutations by nitric oxide are discussed.