Yeast condensin acts as a transient intermolecular crosslinker in entangled DNA

TL;DR

This study reveals that yeast condensin acts as a transient crosslinker in entangled DNA, increasing solution viscosity and elasticity, and influences genome dynamics through its crosslinking activity.

Contribution

It demonstrates that yeast condensin stabilizes DNA entanglements by acting as a transient crosslinker, contrasting previous models of SMC function.

Findings

Yeast condensin binds DNA via hinge and head domains.

Condensin increases viscosity and elasticity of DNA solutions.

ATP fluidifies DNA solutions but does not reduce viscosity.

Abstract

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.