Yeast condensin acts as a transient intermolecular crosslinker in entangled DNA

Fuente: arXiv
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Autori principali: Conforto, Filippo, Valdes, Antonio, Vanderlinden, Willem, Michieletto, Davide
Natura: Preprint
Pubblicazione: 2025
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author Conforto, Filippo
Valdes, Antonio
Vanderlinden, Willem
Michieletto, Davide
author_facet Conforto, Filippo
Valdes, Antonio
Vanderlinden, Willem
Michieletto, Davide
contents Structural-Maintenance-of-Chromosome (SMC) complexes such as condensins organise the folding of chromosomes. However, their role in modulating the entanglement of DNA and chromatin is not fully understood. To address this question, we perform single molecule and bulk characterisation of yeast condensin in entangled DNA. First, we discover that yeast condensin can proficiently bind double-stranded DNA through its hinge domain, in addition to its heads. Through bulk microrheology assays we then discover that physiological concentrations of yeast condensin increase both the viscosity and elasticity of dense solutions of lambda-DNA suggesting that condensin acts as a crosslinker in entangled DNA, stabilising entanglements rather than resolving them and contrasting the popular theoretical picture where SMCs purely drive the formation of segregated, bottle-brush-like chromosome structures. We further discover that the presence of ATP fluidifies the solution -- likely by activating loop extrusion -- but does not recover the viscosity measured in the absence of protein. Finally, we show that the observed rheology can be understood by modelling SMCs as transient crosslinkers in bottle-brush-like entangled polymers. Our findings help us to understand how SMCs affect the dynamics and entanglement of genomes.
format Preprint
id arxiv_https___arxiv_org_abs_2506_04060
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Yeast condensin acts as a transient intermolecular crosslinker in entangled DNA
Conforto, Filippo
Valdes, Antonio
Vanderlinden, Willem
Michieletto, Davide
Soft Condensed Matter
Biological Physics
Structural-Maintenance-of-Chromosome (SMC) complexes such as condensins organise the folding of chromosomes. However, their role in modulating the entanglement of DNA and chromatin is not fully understood. To address this question, we perform single molecule and bulk characterisation of yeast condensin in entangled DNA. First, we discover that yeast condensin can proficiently bind double-stranded DNA through its hinge domain, in addition to its heads. Through bulk microrheology assays we then discover that physiological concentrations of yeast condensin increase both the viscosity and elasticity of dense solutions of lambda-DNA suggesting that condensin acts as a crosslinker in entangled DNA, stabilising entanglements rather than resolving them and contrasting the popular theoretical picture where SMCs purely drive the formation of segregated, bottle-brush-like chromosome structures. We further discover that the presence of ATP fluidifies the solution -- likely by activating loop extrusion -- but does not recover the viscosity measured in the absence of protein. Finally, we show that the observed rheology can be understood by modelling SMCs as transient crosslinkers in bottle-brush-like entangled polymers. Our findings help us to understand how SMCs affect the dynamics and entanglement of genomes.
title Yeast condensin acts as a transient intermolecular crosslinker in entangled DNA
topic Soft Condensed Matter
Biological Physics
url https://arxiv.org/abs/2506.04060