Figure 1.

Basic of DNA Supercoiling. DNA supercoiling is a physical property of the DNA double helix [12], usually ascribed to circular DNA, such as plasmids. Ligation of ends of a linear DNA results in a unconstrained planar circle of duplex DNA made of two strands. Two strands of circular DNA are interlinked and the number of interlinks is called the linking number (LK). LK can only change if one or both DNA strands are transiently cut. The linking number of ‘relaxed’ DNA (Lk₀) reflects the geometry of the double helix: each 10.5 bp of the helical repeat produces one interlink. A relaxed circular DNA with 21 helical turns has Lk = 21. Lk is a function of the twist (Tw) and writhe (Wr): Lk = Tw+Wr. In the first approximation, twist is a measure of the winding of DNA strands around each other. Therefore, for relaxed DNA shown in this figure Lk₀ = Tw₀ = 21 (A, left). Because double helix resists bending and twisting, changing the Tw is compensated by coiling of the double helix axis which is measured by Wr. If the Twist number is altered before ligation, the DNA molecule adopts a supercoiled conformation (A, right). Topologically, immobilizing the end of DNA fragment fixes the number of links between the two DNA strands, mirroring the ligation of DNA fragment to form a circle. Thus, supercoiling can also be imposed on topologically constrained noncircular DNA molecules (b). Negative supercoils (-Sc) is generated by un-twisting (B, right), while positive supercoils (+Sc) is due to over-twisting of double helix (B, left). Supercoiled DNA molecule is under torsional stress. Accordingly, transient propagation of torsional stress along the DNA axis away from its mechanical source results in dynamic supercoiling (c). Although the Lk in topologically constrained DNA cannot be changed without breaking DNA strands, several processes alter distribution of torsional stress along the molecule. Writing part of supercoiling can be manifested as plectoneme, or as toroid when constrained in a nucleosome (d). Constrained supercoiling does not impose torsional stress on adjacent regions until liberated. Torsional stress in negatively supercoiled DNA promotes strand-separation and can be released by formation of melted DNA bubble (e) or by formation of other non-B DNA structures (f). These structures form on tracts of low complexity sequences that are abundant in genomes and occurs at specific genomic locations, supporting a functional role of non-B DNA structures in genomic transactions [2].