The preferential interactions of polylysine and polyarginine with specific base sequences in DNA.

The interaction of nucleic acids with basic proteins and polypeptides has been the subject of numerous studies'-9 motivated in large part by the desire to understand the nature of the complexes formed between nucleic acids and histones, the basic proteins which Stedman and Stedman'0 first suggested might play a role in regulation of the biological activity of DNA. A major question which arises in any discussion of the biological role of histones is whether or not certain histone fractions are capable of interacting preferentially with regions of DNA possessing a special base sequence. From the point of view of the physical chemist, the most relevant observations may be those of Chargaff and his collaborators" 2 and Lucy and Butler.8 These workers found that precipitates formed by the reaction of DNA with histones or polylysine could be redissolved in NaCi solutions of concentrations 1-2 M, and that under these conditions guaninecytosine (G-C)-rich DNA was eluted more readily than was A-T-rich DNA. In this paper, we describe an investigation of the interaction between DNA's of varying base composition and the synthetic polypeptides, polylysine, and polyarginine. We have attempted to carry out the reactions in a manner which would permit us to compare the stabilities of the various complexes, i.e., we have attempted to study the reactions under reversible conditions. At the same time, we have chosen conditions under which the binding forces are relatively weak and differences in selectivity are likely to be enhanced. We find that in solutions about 1M in NaCl concentration, polylysine of degree of polymerization 100 exhibits an almost perfect selectivity for interaction (as judged by preferential precipitation) with A-Trich DNA. Polyarginine interacts about equally with DNA's of base compositions in the range 40-60 per cent GC, but exhibits a slight preference for a DNA of composition 72 per cent GC, and a marked preference for the homopolymer, poly dG: dC.