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Dynamic and facilitated binding of topoisomerase accelerates topological relaxation.

ABSTRACT: 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.

SUBMITTER: Michieletto D

PROVIDER: S-EPMC9071436 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Dynamic and facilitated binding of topoisomerase accelerates topological relaxation.

Michieletto Davide D Fosado Yair A G YAG Melas Elias E Baiesi Marco M Tubiana Luca L Orlandini Enzo E

Nucleic acids research 20220501 8

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 t ...[more]

PMID: 35474478

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Project description:This SuperSeries is composed of the SubSeries listed below.

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