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Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2422-6.

Drug-induced DNA repair: X-ray structure of a DNA-ditercalinium complex.

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  • 1Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.

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.

PMID:
2006181
[PubMed - indexed for MEDLINE]
PMCID:
PMC51244
Free PMC Article
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