Dynamic and Facilitated Binding of Topoisomerase Accelerates Topological Relaxation

TL;DR

This study reveals that the dynamic binding behavior of Topoisomerase II accelerates DNA topological relaxation by enhancing target search efficiency, with implications for understanding DNA topology regulation in biological systems.

Contribution

It introduces a model incorporating the dynamic binding of TopoII, showing how facilitated diffusion accelerates DNA relaxation and influences topological space sampling.

Findings

Dynamic binding speeds up topological relaxation.

Relaxation times are independent of substrate length.

Facilitated diffusion biases lead to faster topological simplification.

Abstract

How type 2 Topoisomerase (TopoII) proteins relax and simplify the topology of DNA molecules is one of the most intriguing open questions in biophysics. Most of the existing models neglect the dynamics of TopoII which is characteristics for 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.