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), 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.
Department of Biochemistry and Molecular Biology, University College London, UK.
T E
TE
Barrett
R
R
Savva
T
T
Barlow
T
T
Brown
J
J
Jiricny
L H
LH
Pearl
D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics; D002945:Cisplatin / Q000737:chemistry*; D003198:Computer Simulation; D003461:Crystallography; D018736:DNA Adducts / Q000737:chemistry*; D004260:DNA Repair; D008958:Models, Molecular; D008968:Molecular Conformation; D009699:N-Glycosyl Hydrolases / Q000737:chemistry* / Q000235:genetics; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry; D044502:Thymine DNA Glycosylase
D001426:Bacterial Proteins; D018736:DNA Adducts; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D009699:N-Glycosyl Hydrolases; D044502:Thymine DNA Glycosylase; C113921:mismatch-specific thymine uracil-DNA glycosylase; D002945:Cisplatin