Nucleophilic Thiol Proteins Bind Covalently to Abasic Sites in DNA

In the course of studies on the enhancement of 1,2-dibromoethane-induced DNA base pair mutations by O⁶-alkylguanine-DNA alkyltransferase (AGT, MGMT), we discovered the facile reaction of AGT with an abasic site in DNA, leading to covalent cross-linking. The binding of AGT differs from the mechanism reported for the protein HMCES; instead it appears to involve formation of a stable thioglycoside. Facile cross-linking was also observed with the protease papain, which like AGT has a low pK_a cysteine, and the tripeptide glutathione.