Fluidification of Entanglements by a DNA Bending Protein.

In spite of the nanoscale and single-molecule insights into nucleoid associated proteins (NAPs), their role in modulating the mesoscale viscoelasticity of entangled DNA has been overlooked so far. By combining microrheology and molecular dynamics simulation, we find that the abundant NAP "integration host factor" (IHF) lowers the viscosity of entangled λDNA 20-fold at physiological concentrations and stoichiometries. Our results suggest that IHF may play a previously unappreciated role in resolving DNA entanglements and in turn may be acting as a "genomic fluidizer" for bacterial genomes.

Dynamic and facilitated binding of topoisomerase accelerates topological relaxation.

How type 2 Topoisomerase (TopoII) proteins relax and simplify the topology of DNA molecules is one of the most intriguing open questions in genome and DNA biophysics. Most of the existing models neglect the dynamics of TopoII which is expected of proteins searching their targets via facilitated diffusion. Here, we show that dynamic binding of TopoII speeds up the topological relaxation of knotted substrates by enhancing the search of the knotted arc. Intriguingly, this in turn implies that the timescale of topological relaxation is virtually independent of the substrate length. We then discover that considering binding biases due to facilitated diffusion on looped substrates steers the sampling of the topological space closer to the boundaries between different topoisomers yielding an optimally fast topological relaxation. We discuss our findings in the context of topological simplification in vitro and in vivo.

Nonequilibrium dynamics and action at a distance in transcriptionally driven DNA supercoiling.

We study the effect of transcription on the kinetics of DNA supercoiling in three dimensions by means of Brownian dynamics simulations of a single-nucleotide-resolution coarse-grained model for double-stranded DNA. By explicitly accounting for the action of a transcribing RNA polymerase (RNAP), we characterize the geometry and nonequilibrium dynamics of the ensuing twin supercoiling domains. Contrary to the typical textbook picture, we find that the generation of twist by RNAP results in the formation of plectonemes (writhed DNA) some distance away. We further demonstrate that this translates into an "action at a distance" on DNA-binding proteins; for instance, positive supercoils downstream of an elongating RNAP destabilize nucleosomes long before the transcriptional machinery reaches the histone octamer. We also analyze the relaxation dynamics of supercoiled double-stranded DNA, and characterize the widely different timescales of twist diffusion, which is a simple and fast process, and writhe relaxation, which is much slower and entails multiple steps.