Spontaneous Unidirectional Loop Extrusion Emerges from Symmetry Breaking of SMC Extension

Abstract: DNA loop extrusion is arguably one of the most important players in genome organization. The precise mechanism by which loop extruding factors (LEFs) work is still unresolved and much debated. One of the major open questions in this field is how do LEFs establish and maintain unidirectional motion along DNA. In this paper, we use High-Speed AFM data to show that condensin hinge domain displays a structural, geometric constraint on the angle within which it can extend with respect to the DNA-bound domains. Using computer simulations, we then show that such a geometrical constraint results in a local symmetry breaking and is enough to rectify the extrusion process, yielding unidirectional loop extrusion along DNA. Our work highlights an overlooked geometric aspect of the loop extrusion process that may have a universal impact on SMC function across organisms.