title: Drug-induced DNA repair: X-ray structure of a DNA-ditercalinium complex.
abstract: Ditercalinium is a synthetic anticancer drug that binds to DNA by bis-intercalation and activates DNA repair processes. In prokaryotes, noncovalent DNA-ditercalinium complexes are incorrectly recognized by the uvrABC repair system as covalent lesions on DNA. In eukaryotes, mitochondrial DNA is degraded by excess and futile DNA repair. Using x-ray crystallography, we have determined, to 1.7 A resolution, the three-dimensional structure of a complex of ditercalinium bound to the double-stranded DNA fragment [d(CGCG)]2. The DNA in the complex with ditercalinium is kinked (by 15 degrees) and severely unwound (by 36 degrees) with exceptionally wide major and minor grooves. Recognition of the DNA-ditercalinium complex by uvrABC in prokaryotes, and by mitochondrial DNA repair systems in eukaryotes, might be related to drug-induced distortion of the DNA helix.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
authors.forename: Q
authors.initials: Q
authors.lastname: Gao
authors.forename: L D
authors.initials: LD
authors.lastname: Williams
authors.forename: M
authors.initials: M
authors.lastname: Egli
authors.forename: D
authors.initials: D
authors.lastname: Rabinovich
authors.forename: S L
authors.initials: SL
authors.lastname: Chen
authors.forename: G J
authors.initials: GJ
authors.lastname: Quigley
authors.forename: A
authors.initials: A
authors.lastname: Rich
mesh_terms: D001483:Base Sequence; D002227:Carbazoles / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry* / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects*; D007364:Intercalating Agents / Q000494:pharmacology; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D002227:Carbazoles; D007364:Intercalating Agents; D009838:Oligodeoxyribonucleotides; D004247:DNA; C042804:ditercalinium