Cohesin supercoils DNA during loop extrusion

Abstract

AbstractCohesin extrudes genomic DNA into loops that promote chromatin assembly, gene regulation and recombination. Here we show that cohesin introduces negative supercoils into extruded DNA. Supercoiling requires engagement of cohesin’s ATPase heads, DNA clamping by these heads, and a DNA binding site on cohesin’s hinge, indicating that cohesin supercoils DNA when constraining it between the hinge and the clamp. Our results suggest that DNA extrusion stops once cohesin reaches its stall torque during supercoiling, and a cohesin mutant predicted to stall at lower torque forms shorter loops in cells. These results indicate that supercoiling is an integral part of the loop extrusion mechanism and that cohesin controls genome architecture not only by looping DNA but also by supercoiling it.