Plectoneme tip bubbles: Coupled denaturation and writhing in supercoiled DNA

Abstract

Biological information is not only stored in the digital chemical sequence of double helical DNA, but is also encoded in the mechanical properties of the DNA strands, which can influence biochemical processes involving its readout. For example, loop formation in the Lac operon can regulate the expression of key genes, and DNA supercoiling is closely correlated to rhythmic circardian gene expression in cyanobacteria. Supercoiling is also important for large scale organisation of the genome in both eukaryotic and prokaryotic cells. DNA can respond to torsional stress by writhing to form looped structures called plectonemes, thus transferring energy stored as twist into energy stored in bending. Denaturation bubbles can also relax torsional stress, with the enthalpic cost of breaking bonds being compensated by their ability to absorb undertwist. Here we predict a novel regime where bubbles form at the tips of plectonemes, and study its properties using coarse-grained simulations. These tip bubbles can occur for both positive and negative supercoiling and greatly reduce plectoneme diffusion by a pinning mechanism. They can cause plectonemes to preferentially localise to AT rich regions, because bubbles more easily form there. The tip-bubble regime occurs for supercoiling densities and forces that are typically encountered for DNA in vivo, and may be exploited for biological control of genomic processes.