Monday, 23 May 2005
339

This presentation is part of: Biological Chemistry Posters

Different translesion bypass of guanine–N2 monoadducts of mitomycin C and guanine-N7 monoadducts of 2,7-diaminomitosene by eta, Klenow exo-, Klenow exo+ and T7 exo- DNA polymerases

Cristina C. Clement, Hunter College, City University of New York (CUNY), NYC, NY and Maria Tomasz, Hunter College, City University of New York (CUNY), NYC, NY.

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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