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Comparative Error-Free And Error-Prone Translesion Synthesis Of N2‑2′-Deoxyguanosine Adducts Formed By Mitomycin C And Its Metabolite, 2,7-Diaminomitosene, In Human Cells, Arindam Bose, Chaitra Surugihalli, Paritosh Pande, Elise Champeil, Ashis K. Basu

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Mitomycin C (MC) is a cytotoxic and mutagenic antitumor agent that alkylates DNA upon reductive activation. 2,7-Diaminomitosene (2,7-DAM) is a major metabolite of MC in tumor cells, which also alkylates DNA. MC forms seven DNA adducts, including monoadducts and inter- and intrastrand cross-links, whereas 2,7-DAM forms two monoadducts. Herein, the biological effects of the dG-N2 adducts formed by MC and 2,7-DAM have been compared by constructing single-stranded plasmids containing these adducts and replicating them in human embryonic kidney 293T cells. Translesion synthesis (TLS) efficiencies of dG-N2-MC and dG-N2-2,7-DAM were 38 ± 3 and 27 …