Sequence Dependent Structural Transitions in DNA Induced by Torque

Abstract

B-DNA becomes unstable under superhelical stress and is able to adopt a wide range of alternative conformations including Z-DNA, cruciforms, and strand-separated DNA. Localized sequence-dependent destabilization of superhelical DNA is thought to be important for the regulation of biological processes requiring strand separation, such as transcription and replication initiation. To directly probe the effect of sequence on structural transitions driven by torque, we have measured the torsional response of a panel of DNA sequences using newly developed extensions of the rotor bead tracking assay1. In these assays, a submicron rotor bead is employed as a rotational probe attached to the side of a single stretched DNA molecule. Plots of torque as a function of twist show clear signatures of sequence-dependent cooperative structural transitions. Our results shed new light on the structure and stability of mismatched DNA sequences as well as the torsional properties of replication origins.1. Bryant, Z. et al. Nature Vol. 424 338-41 (2003).