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. 1990 Apr 25;18(8):1983–1989. doi: 10.1093/nar/18.8.1983

Distamycin inhibition of topoisomerase I-DNA interaction: a mechanistic analysis.

U H Mortensen 1, T Stevnsner 1, S Krogh 1, K Olesen 1, O Westergaard 1, B J Bonven 1
PMCID: PMC330672  PMID: 2159632

Abstract

Inhibition of eukaryotic DNA topoisomerase I by the minor groove binding ligand, distamycin A, was investigated. Low concentrations of the ligand selectively prevented catalytic action at a high affinity topoisomerase I binding sequence. A restriction enzyme protection assay indicated that the catalytic cycle was blocked at the binding step. Distamycin binding sites on DNA were localized by hydroxyl radical footprinting. A strongly preferred site mapped to a homopolymeric (dA).(dT)-tract partially included in the essential topoisomerase I binding region. Mutational elimination of the stable helix curvature associated with this ligand binding site demonstrated that (i) the intrinsic bend was unessential for efficient binding of topoisomerase I, and (ii) distamycin inhibition did not occur by deformation of a stable band. Alternative modes of inhibition are discussed.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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