STRUCTURE OF A DNA BASE-EXCISION PRODUCT RESEMBLING A CISPLATIN INTER-STRAND ADDUCT

Base-excision of a self-complementary oligonucleotide with central G:T mismatches by the G:T/U-specific mismatch DNA glycosylase (MUG), gene rates an unusual DNA structure which is remarkably similar in conforma tion to an interstrand DNA adduct of the anti-tumor drug cis-diammined ichloro-platinum. The abasic sugars generated by excision of the misma tched thymines are extruded from the double-helix, and the 'widowed' d eoxyguanosines rotate so that their N7 and O6 groups protrude into the minor groove of the duplex and restack in an interleaved intercalativ e geometry, generating a kink in the helix axis.