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Ligand-Induced DNA Condensation: Choosing the Model

Laboratory of Nucleoprotein Biophysics and Biochemistry, Institute of Bioorganic Chemistry, Belarus National Academy of Sciences, Minsk, Belarus; and Groupe de Biophysique de DNA, Département de Biologie Joliot-Curie/Service de Biochimie et de Génétique Moléculaire, Commissariat à l'Energie Atomique/Saclay, Gif-sur-Yvette, France

Correspondence: Address reprint requests to Vladimir Teif, Tel.: 375-17-264-8263; Fax: 375-17-264-8647; E-mail: teif{at}iboch.bas-net.by.

We test and compare different models for ligand-induced DNA condensation. Using ¹⁴C-labeled spermidine³⁺, we measure the binding to condensed DNA at micromolar to molar polyamine concentrations. DNA aggregates at a critical polyamine concentration. Spermidine³⁺ binding becomes highly cooperative at the onset of aggregation. At higher concentrations, spermidine³⁺ binding to condensed DNA reaches a plateau with the degree of binding equal to 0.7 (NH⁴⁺/PO^3–). Condensed DNA exists in a wide range of spermidine concentrations with the roughly constant degree of ligand binding. At greater concentrations, the degree of binding increases again. Further spermidine penetration between the double helices causes DNA resolubilization. We show that a simple two-state model without ligand-ligand interactions qualitatively predicts the reentrant aggregation-resolubilization behavior and the dependence on the ligand, Na⁺, and DNA concentrations. However, such models are inconsistent with the cooperative ligand binding to condensed DNA. Including the contact or long-range ligand-ligand interactions improves the coincidence with the experiments, if binding to condensed DNA is slightly more cooperative than to the starting DNA. For example, in the contact interaction model it is equivalent to an additional McGhee-von Hippel cooperativity parameter of 2. Possible physical mechanisms for the observed cooperativity of ligand binding are discussed.

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