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.

Automated summary

This study explores how type 2 Topoisomerase (TopoII) proteins enhance the relaxation of DNA molecules by speeding up the topological search and optimizing the sampling of the topological space. The findings suggest that the time scale of topological relaxation is independent of the substrate length. These results are significant for understanding the role of DNA topological simplification in vitro and in vivo.