Human O6-alkylguanine-DNA alkyltransferase fails to repair O4-methylthymine and methyl phosphotriesters in DNA as efficiently as does the alkyltransferase from Escherichia coli.

The repair of alkylated poly(dT) annealed to poly(dA) and alkylated DNA was studied using human cells in culture, extracts of human liver and Escherichia coli, and partially purified O6-alkylguanine-DNA alkyltransferase from human liver. The human alkyltransferase behaved as if the transferring and accepting functions of the repair process resided on the same molecule. Extracts of E. coli efficiently repaired O6-methylguanine, O4-methylthymine and methyl phosphotriesters in DNA. In contrast, cultured human cells and extracts from human liver repaired O6-methylguanine but did not repair O4-methylthymine or methyl phosphotriesters in DNA nearly as efficiently as did the E. coli extracts.