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A universal description for the experimental behavior of salt-(in)dependent oligocation-induced DNA condensation

Korolev, Nikolay, Berezhnoy, Nikolay V., Eom, Khee Dong, Tam, James P., Nordenskiöld, Lars
Nucleic acids research 2009 v.37 no.21 pp. 7137-7150
absorption, calorimetry, chromatin, dissociation, equations, ligands, light scattering, median effective concentration, plasmids, potassium chloride, titration
We report a systematic study of the condensation of plasmid DNA by oligocations with variation of the charge, Z, from +3 to +31. The oligocations include a series of synthetic linear ε-oligo(L-lysines), (denoted εKn, n = 3-10, 31; n is the number of lysines equal to the ligand charge) and branched α-substituted homologues of εK10: εYK10, εLK10 (Z = +10); εRK10, εYRK10 and εLYRK10 (Z = +20). Data were obtained by light scattering, UV absorption monitored precipitation assay and isothermal titration calorimetry in a wide range concentrations of DNA and monovalent salt (KCl, CKCl). The dependence of EC₅₀ (ligand concentration at the midpoint of DNA condensation) on CKCl shows the existence of a salt-independent regime at low CKCl and a salt-dependent regime with a steep rise of EC₅₀ with increase of CKCl. Increase of the ligand charge shifts the transition from the salt-independent to salt-dependent regime to higher CKCl. A novel and simple relationship describing the EC₅₀ dependence on DNA concentration, charge of the ligand and the salt-dependent dissociation constant of the ligand-DNA complex is derived. For the ε-oligolysines εK3-εK10, the experimental dependencies of EC₅₀ on CKCl and Z are well-described by an equation with a common set of parameters. Implications from our findings for understanding DNA condensation in chromatin are discussed.