Loop Extrusion Reversal by Condensin Motor is Mediated by Catch Bonds

TL;DR

This study develops a stochastic model to explain how condensin, a genome-folding motor, exhibits catch bond behavior, influencing loop extrusion dynamics under mechanical force.

Contribution

It introduces a theory that accounts for force-dependent stepping and reveals catch bond-like states in condensin, expanding understanding of genome organization mechanisms.

Findings

Force increases the lifetime of an intermediate state in condensin's cycle.

Condensin exhibits catch bond-like behavior at sub-piconewton forces.

The model quantitatively explains measured step size and dwell time distributions.

Abstract

Structural Maintenance Complexes (SMC) are energy consuming motors that are important in folding the genome by loop extrusion (LE) in all stages of the cell cycle. Single molecule magnetic tweezer pulling experiments have revealed that condensin, a member of the SMC family involved in mitosis, takes occasional backward steps, thus coughing up the gains in the length of the extruded loop. To reveal the mechanism of the forward and backward steps simultaneously, we developed a theory using the stochastic kinetic model and the scrunching mechanism for LE. The calculations quantitatively account for the measured force-dependent step size and dwell time distributions in both the directions. By postulating the existence of an intermediate state in the ATP-driven cycle that is poised to take a forward or a backward step, we predict that its lifetime increases as the external mechanical force increases till a critical value and subsequently decreases at higher forces. The surprising finding of lifetime increase in an active motor, at sub-piconewton forces, is the characteristic of catch bonds, known in force-induced rupture of several passive protein complexes. The identification of catch bond-like states in condensin not only expands our understanding of LE but also highlights the significance of mechanical forces in regulating genome organization.