DNA forms supercoiled regions in an otherwise relaxed state due to torsional strain that is generated because of the twisting of the DNA helix. The supercoiling is of two types: positive supercoiling, in which the DNA helix undergoes over-winding, and negative supercoiling, in which the DNA helix undergoes under-winding. This supercoiling of the DNA plays a crucial role in maintaining its compactness, stability, replication, transcription, etc. Two parameters, Twist (T) and Writhe (W), have been used to quantify the extent of supercoiling. While T refers to the number of helical turns in one DNA strand around the other within the double helix, W is the number of times the double helix crosses over on itself. Adding the two parameters (i.e., T + W) provides us with the linking number (referred to as “L”) that defines the overall topology of the DNA. The torsional stress is not distributed homogeneously along the length of a DNA molecule but is organized into independent topological domains. The neighboring topological domains are rarely contiguous but are separated by barriers created by macromolecules, including proteins. Furthermore, the distribution of torsional stress within a topological domain is altered by several families of molecules. Circular DNAs often exist in a supercoiled conformation called a “plectoneme,” in which the DNA duplex is wound around another part of the same molecule to form a higher-order helix.

In the study by Marc Joyeux, Brownian dynamics simulation has been used to discover how plectonemes form, evolve, and eventually die during transcription. Simulations revealed that the two sides of RNA polymerase (RNAP) transcribing a supercoiled DNA are not equivalent; the upstream side of the RNAP binding site is significantly less cluttered than its downstream side. The main feature of the dynamics of plectonemes on torsionally relaxed DNA chains is the asymmetric formation of negatively and positively supercoiled plectonemes. The negatively supercoiled plectonemes form and grow at the upstream side of the RNAP, whereas the positively supercoiled ones grow quite far ahead of the RNAP, a feature known as “twin supercoiled domain” (TSD). This asymmetry is even more pronounced for negatively supercoiled DNA molecules, which are most common in prokaryotes, in the sense that only negatively supercoiled plectonemes form at the upstream side of the RNAP. In both cases, negatively supercoiled plectonemes detach from the RNAP after reaching a size of several thousand base pairs and destabilize rapidly as their distance to the RNAP increases.

Moreover, the simulations reveal that the transcribing RNAP is responsible for systematic arrays of DNA contacts, which extend several thousand base pairs away from it. The simulations also confirm that the topological barriers significantly perturb the dynamics of TSDs. The work might be useful in determining the internal organization of bacterial nucleoids and other similar superstructures of DNAs.