SMC Motor Proteins Operate at the Near-Minimal Forces for DNA Loop Extrusion

Abstract

Loop extrusion by structural maintenance of chromosomes (SMC) complexes is essential for genome organization, yet the forces driving this process remain poorly understood. We present a coarse-grained model enabling predictive simulations of in vitro loop extrusion experiments at experimentally relevant time and length scales by matching parameters with concrete experiments. Using this model, we demonstrate that the extrusion forces generated by SMC motor proteins are just sufficient to overcome initial entropic barriers and sustain loop extrusion, highlighting that motors operate in the thermal regime. By measuring stalling tension directly, we confirm that they can be reliably determined by the Marko-Siggia equation and that varying grafting distances in experimental setups has only a marginal effect on the resulting tension. These results provide a predictive computation method for dissecting the mechanics of SMC driven genome folding.