The guanine (G)-N2 DNA monoadduct of mitomycin C (MC), a cytotoxic anticancer drug, inhibits translesion bypass by DNA polymerases. The non-cytotoxic MC metabolite 2,7-diaminomitosene (2,7-DAM) forms a G-N7 DNA monoadduct in vitro and in vivo. We tested a potential correlation between the relative ease of bypass of this adduct and the lack of cytotoxicity of 2,7-DAM. In a 24 mer template/15 mer primer system the G-N7-2,7-DAM adduct was bypassed by all four polymerases, resulting in the production of a fully extended primer. The extension was at a slower rate as compared with the control, non-alkylated template. Klenow exo- has the highest efficiency of bypassing the lesion followed by T7 exo-, klenow exo+ with the lowest efficiency being observed for eta polymerase. In sharp contrast, the G-N2-MC monoadduct was not bypassed beyond the adduct position by none of the four polymerases.
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