Energetics of twisted DNA topologies

Abstract

Our goal is to review the main theoretical models used to calculate free energy changes associated with common, torsion-induced conformational changes in DNA and provide the resulting equations hoping to facilitate quantitative analysis of both in vitro and in vivo studies. This review begins with a summary of work regarding the energy change of the negative supercoiling-induced B- to L-DNA transition, followed by a discussion of the energetics associated with the transition to Z-form DNA. Finally, it describes the energy changes associated with the formation of DNA curls and plectonemes, which can regulate DNA-protein interactions and promote cross talk between distant DNA elements, respectively. The salient formulas and parameters for each scenario are summarized in table format to facilitate comparison and provide a concise, user-friendly resource.

Figure 1

Sketches of the twin-domain model and plectoneme formation. (A) During transcription of a template that is torsionally constrained at each end, negative supercoiling accumulates upstream and positive supercoiling accumulates downstream. This RNA-polymerase-generated supercoiling can produce plectonemes, although negative supercoiling may induce DNA melting or transition to the L- or Z-form before plectonemes are formed at the buckling transition. Transcription is not the only supercoil-generating process in the cell, but it is used here as an example. (B) Unwinding DNA may produce a “soliton” in which the DNA curls about the long axis without significantly changing the tether length. Detectable tether length changes result when the curl aligns perpendicular to the direction of extension and subsequently twists to form a plectoneme.

Figure 2

Schematic representation of the interplay between torsion-generating DNA transactions, such as transcription, conformational and topological changes in DNA, and protein binding. DNA-enzyme-induced torsional stress causes local and long-range DNA conformational changes that include DNA melting, B to L or Z transition, major and minor groove changes, curls, and plectoneme formation. This affects protein binding. For example, plectonemes facilitate the juxtaposition of binding sites for looping proteins. Also, DNA bending, kinking, melting or B-L or Z transition can affect the energy barrier required for specific DNA-binding proteins or motors to process DNA.