Ligand-induced DNA condensation: choosing the model

¹ Natl. Acad. Sci. (Belarus) and CEA/Saclay (France)

^* To whom correspondence should be addressed. E-mail: vlad_teif{at}yahoo.com.

Submitted on April 1, 2005
Revised on May 9, 2005
Accepted on 18 July 2005

	Abstract

We test and compare different models for ligand-induced DNA condensation. Using ¹⁴C labelled 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⁺ / PO₃^-). 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 predicts qualitatively 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 then to the starting DNA. For example, in the contact interaction model it is equivalent to an additional McGhee-von Hippel cooperativity parameter of about 2. Possible physical mechanisms for the observed cooperativity of ligand binding are discussed.

Key Words: DNA condensation, aggregation, cooperative binding, ligand-DNA interaction, phase transition, spermidine

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