Twisting DNA by Salt

DNA structure and properties sensitively depend on its environment, in particular on the ion atmosphere. One of the most fundamental properties of DNA is its helicity and here we investigate how it changes with concentration and identity of the surrounding ions. To resolve how metal cations influence the helical twist, we have combined magnetic tweezer experiments and extensive all-atom molecular dynamics simulations. Two interconnected trends are observed for monovalent alkali and divalent alkaline earth cations. First, DNA twist increases with increasing ion concentration. Secondly, for a given salt concentration, DNA twist strongly depends on cation identity. Metal cations with high charge density (such as Li+ or Ca2+) are most efficient at inducing DNA twist and lead to overwinding. By contrast, metals with intermediate charge density (such as Na+ or Ba2+) reduce the twist and underwind the helix compared to higher density ions. Our molecular dynamics simulations reveal that preferential binding of the metals to the DNA backbone and the nucleobases has opposing effects on DNA twist and provide a microscopic explanation of the observed ion specificity. The comprehensive view gained from our combined approach provides a foundation to understand and predict metal-induced structural changes in nature or in DNA nanotechnology.

A twist defect mechanism for ATP-dependent translocation of nucleosomal DNA

As superfamily 2 (SF2)-type translocases, chromatin remodelers are expected to use an inchworm-type mechanism to walk along DNA. Yet how they move DNA around the histone core has not been clear. Here we show that a remodeler ATPase motor can shift large segments of DNA by changing the twist and length of nucleosomal DNA at superhelix location 2 (SHL2). Using canonical and variant 601 nucleosomes, we find that the Saccharomyces cerevisiae Chd1 remodeler decreased DNA twist at SHL2 in nucleotide-free and ADP-bound states, and increased twist with transition state analogs. These differences in DNA twist allow the open state of the ATPase to pull in ~1 base pair (bp) by stabilizing a small DNA bulge, and closure of the ATPase to shift the DNA bulge toward the dyad. We propose that such formation and elimination of twist defects underlie the mechanism of nucleosome sliding by CHD-, ISWI-, and SWI/SNF-type remodelers.