Properties of DNA in concentrated aqueous solutions of LiCl suggest transition to C-DNA

C-DNA represents a canonical DNA form related to B-DNA. While C-DNA is known to exist in air-dried fibers, its occurrence in aqueous solutions remains subject to debate. In fibers, the transition from B- to C-DNA is promoted by reduced hydration in the presence of certain monovalent cations (most notably Li+), and this process is generally associated with an increase in the helical twist. To understand if the B-to-C transition can occur in liquid media in principle, we analyzed properties of several circular DNA substrates in aqueous solutions with varying concentrations of LiCl (0.1-8 M). To this end, we estimated changes in the helical twist directly from circular dichroism (CD) spectra of a large supercoiled plasmid and, in parallel, assayed conformational changes in DNA minicircles by atomic force microscopy (AFM). We found that the helical twist increased continuously over the entire range of tested LiCl concentrations, without being subject to saturation even at 8 M LiCl. The overall increase in the helical twist was compatible with the B-to-C transition occurring in solution at a concentration of LiCl of about 8 M, suggesting that C-DNA should be stable above this level.