Structure of a DNA base-excision product resembling a cisplatin inter-strand adduct

Abstract

Base-excision of a self-complementary oligonucleotide with central G:T mismatches by the G:T/U-specific mismatch DNA glycosylase (MUG), generates an unusual DNA structure which is remarkably similar in conformation to an interstrand DNA adduct of the anti-tumor drug cis-diamminedichloroplatinum. The abasic sugars generated by excision of the mismatched thymines are extruded from the double-helix, and the 'widowed' deoxyguanosines rotate so that their N7 and O6 groups protrude into the minor groove of the duplex and restack in an interleaved intercalative geometry, generating a kink in the helix axis.