title: Chiral electrostatics breaks the mirror symmetry of DNA supercoiling.
abstract: DNA supercoiling plays a fundamental role in regulating cellular activity and in the packaging of genetic material. In this communication, we analyse the effect of attractive chiral forces on the conformation of a closed circular DNA molecule, arising due to the helical patterns of charges on the DNA. We propose a model for closed loop DNA which uses the results of the recent theory of electrostatic interactions of a braid of two free-ended DNA molecules. Our model reproduces the known features of DNA supercoiling in an environment of low ionic strength. In high salt conditions, and in the presence of counterions that have high affinity to the DNA grooves, helix-specific forces significantly affect the conformation of the molecule by favouring a state characterized by a central left-handed braided section where there is close contact between distant portions of the loop. In such an environment we predict a previously unexplored possibility that nicked or topologically relaxed DNA molecules adopt a writhed state. This prediction suggests an alternative explanation for experiments in which it was assumed that the most stable topoisomer is always an open circle. Our results also give the first plausible explanation for the occurrence of tightly interwound molecules observed in cryo-electron microscopy and atomic force microscopy in a high ionic strength environment. We suggest several new experiments to test the predictions of this theory.
authors.affiliation: Chemistry Department, Faculty of Natural Sciences, Imperial College London, London, UK. ruggero.cortini@gmail.com
authors.forename: R
authors.initials: R
authors.lastname: Cortini
authors.forename: D J
authors.initials: DJ
authors.lastname: Lee
authors.forename: A
authors.initials: A
authors.lastname: Kornyshev
mesh_terms: D004278:DNA, Superhelical / Q000737:chemistry*; D004573:Electrolytes / Q000737:chemistry; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D055672:Static Electricity; D013237:Stereoisomerism
chemical_list: D004278:DNA, Superhelical; D004573:Electrolytes