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.

• Authors: T E Barrett, R Savva, T Barlow, T Brown, J Jiricny, L H Pearl
• Journal: Nature structural biology (Nat Struct Biol) Vol. 5 Issue 8 Pg. 697-701 (Aug 1998) ISSN: 1072-8368 [Print] United States
• PMID: 9699633 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bacterial Proteins
• DNA Adducts
• Oligodeoxyribonucleotides
• Recombinant Proteins
• N-Glycosyl Hydrolases
• Thymine DNA Glycosylase
• mismatch-specific thymine uracil-DNA glycosylase
• Cisplatin

Topics

• Bacterial Proteins (chemistry, genetics)
• Cisplatin (chemistry)
• Computer Simulation
• Crystallography
• DNA Adducts (chemistry)
• DNA Repair
• Models, Molecular
• Molecular Conformation
• N-Glycosyl Hydrolases (chemistry, genetics)
• Oligodeoxyribonucleotides (chemistry)
• Recombinant Proteins (chemistry)
• Thymine DNA Glycosylase