CN09-02

Formamidopyrimidine lesions can arise from either oxidative or alkylative damage to purines. We have developed chemistry for the site-specific incorporation of N6-(2-deoxy-D-erythropentofuranosyl)-2,6-diamino-4-hydroxy-5-N-methylformamidopyrimidine (MeFAPy-dG) into oligonucleotides. This lesion is derived from the initial N7-methylation of dG followed by hydroxide induced imidazole ring opening. The in vitro by-pass of the MeFAPy-dG lesion was examined by prokaryotic and human Y-family DNA polymerases; the by-pass products were characterized by tandem mass spectrometry. The MeFAPy-dG lesion was found to be highly miscoding.

Sixth AACR International Conference on Frontiers in Cancer Prevention Research-- Dec 5-8, 2007; Philadelphia, PA