Drug-induced DNA repair: X-ray structure of a DNA-ditercalinium complex.
Year: 1991
Type: article
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: Q Gao, L D Williams, M Egli, D Rabinovich, S L Chen, G J Quigley, A Rich
Institution: Massachusetts Institute of Technology
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2053929263