Drug binding by branched DNA molecules: analysis by chemical footprinting of intercalation into an immobile junction
- 16 January 1990
- journal article
- research article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 29 (2) , 570-578
- https://doi.org/10.1021/bi00454a034
Abstract
Branched DNA structures interact with drugs differently from unbranched control duplexes of similar sequence. A specific interaction between the reagent (methidiumpropyl-EDTA) .cntdot. Fe(II) [MPE .cntdot. Fe(II)] and a branched DNA molecule formed from 16-mer oligonucleotide strands has been reported [Guo, Q., Seeman, N. C., and Kallenbach, N. R. (1989) Biochemistry 28, 2355-2359]. The structure of the branched molecule is thought to be made up of two double-helical stacking domains with an overall twofold symmetry across the branch site. The MPE-Fe(II) interaction occurs predominantly at or adjacent to the branch site and is eliminated by a second intercalator, propidium iodide. Further studies on the nature and properties of this site are presented here. Comparison of the patterns of scission of linear duplex and branched tetramer by EDTA .cntdot. Fe(II), MPE .cntdot. Fe(II), and Cu(I)-(o-phenanthroline)2 [(OP)2Cu(I)] provides a higher resolution picture of the site of enhanced binding. In particular, the sensitive footprinting afforded by (OP)2Cu(I) allows us to localize the major site of preferential interaction with propidium precisely to the branch point itself, with a roughly twofold symmetric pattern of cuts resulting. In detail, the differential pattern with respect to each duplex control is distinct for each arm of the junction. Excess propidium results in apparent reversal of the crossover isomer of the junction, indicating a possible additional avenue for the action of drugs in biological systems-effects on the products of recombination.This publication has 31 references indexed in Scilit:
- Secondary structure specificity of the nuclease activity of the 1,10-phenanthroline-copper complex.Proceedings of the National Academy of Sciences, 1984
- Sequence-specific double-strand cleavage of DNA by penta-N-methylpyrrolecarboxamide-EDTA X Fe(II).Proceedings of the National Academy of Sciences, 1983
- Design of immobile nucleic acid junctionsBiophysical Journal, 1983
- Nucleic acid junctions and latticesJournal of Theoretical Biology, 1982
- Origin of malondialdehyde from DNA degraded by Fe(II) x bleomycin.Journal of Biological Chemistry, 1980
- Hydrogen-deuterium exchange analysis of ligand-macromolecule interactions: ethidium-deoxyribonucleic acid systemBiochemistry, 1980
- Analysis of cooperativity and ion effects in the interaction of quinacrine with DNABiopolymers, 1979
- Contacts between the lac repressor and the thymines in the lac operator.Proceedings of the National Academy of Sciences, 1977
- A new method for sequencing DNA.Proceedings of the National Academy of Sciences, 1977
- Studies of the binding of actinomycin and related compounds to DNAJournal of Molecular Biology, 1968