Enzymatic properties of Escherichia coli and human 7,8-dihydro-8-oxoguanine DNA glycosylases

Oxidative damage to DNA generates aberrant guanine bases such as 2,6diamino-4-hydroxy-formamidopyrimidine (Fapy) and 7,8-dihydro-8oxoguanine (8-oxoG). Although synthetic oligonucleotides containing a single 8-oxoG have been widely used to study enzymatic processing of this lesion, the synthesis of oligonucleotides containing Fapy as a unique lesion has not been achieved to date. In this study, an oligonucleotide containing a single 2,6-diamino-4hydroxy-5-(N-methyl)formamidopyrimidine (me-Fapy, a methylated derivative of Fapy) was prepared by a DNA polymerase reaction and the subsequent alkali treatment. The repair activity of Fpg and hOGGl proteins were compared using oligonucleotide substrates containing me-Fapy and 8oxoG.