DNA compaction in viral capsids or chromosomes combines high density and curvature. The microscopic forces governing these assemblies are poorly understood. Shape matters in the interactions at work. Helices in compact assemblies are thus predicted to correlate, as widely documented by theoretical works and simulations. In contrast the phenomenon is poorly documented experimentally. In addition, helical correlations are not compatible with curvature, a general feature of DNA dense states in vitro and in vivo.
Using cryo electron microscopy of DNA toroids self-assembled upon DNA condensation in vitro, we analyzed correlations between DNA double helices, focusing on the relationship between curvature and helical correlations. We find that in-phase helical correlations are preferred within a wide range of experimental conditions. This preferred interaction leads to nucleation of radial alignments, that propagate and reshape the toroid into pentagons and tetragons, with curvature concentrated within narrow sectors. There, we report a decrease of the helical pitch of the DNA molecule, which could correspond to a B to A transition, a transition so far obtained in dehydrated forms of DNA, and induced here by the interplay between correlations and curvature.
Altogether, this work reveals how intermolecular interactions, through preferred phasing of helices, tunes both the shape of the supramolecular assembly (at the mesoscale) and the conformation of the double helix (at the nanoscale). These phenomena can be expected at work within a broad range of biological and nanoengineering contexts, from DNA architectures in viral capids, toroidal bacterial nucleoids, or cylindrical spermatozoa, and even more generally, upon close approach of doubles helices, including molecular recognition, to design of materials such as DNA origami.
The work is published in Nucleic Acid Research.
Vertchik, K., Bony, S., Taiki, F., Degrouard, J., Victor, J. M., & Leforestier, A. (2025). Helical correlations in curved DNA condensates. Nucleic Acids Research, 53(19), gkaf989.