biostudies-literatureUnknown616(7958)Pradhan BStructural maintenance of chromosomes (SMC) protein complexes are essential for the spatial organization of chromosomes¹. Whereas cohesin and condensin organize chromosomes by extrusion of DNA loops, the molecular functions of the third eukaryotic SMC complex, Smc5/6, remain largely unknown². Using single-molecule imaging, we show that Smc5/6 forms DNA loops by extrusion. Upon ATP hydrolysis, Smc5/6 reels DNA symmetrically into loops at a force-dependent rate of one kilobase pair per second. Smc5/6 extrudes loops in the form of dimers, whereas monomeric Smc5/6 unidirectionally translocates along DNA. We also find that the subunits Nse5 and Nse6 (Nse5/6) act as negative regulators of loop extrusion. Nse5/6 inhibits loop-extrusion initiation by hindering Smc5/6 dimerizaNature843-848https://www.ebi.ac.uk/biostudies/studies/S-EPMC10132971biostudies-literatureThe Smc5/6 complex is a DNA loop-extruding motor.PMC10132971Bjorkegren CPradhan BKanno TKim EUmeda Igarashi MWong JSKJeppsson KLoke MSBaaske MDfalseThe Smc5/6 complex is a DNA loop-extruding motor.Structural maintenance of chromosomes (SMC) protein complexes are essential for the spatial organization of chromosomes¹. Whereas cohesin and condensin organize chromosomes by extrusion of DNA loops, the molecular functions of the third eukaryotic SMC complex, Smc5/6, remain largely unknown². Using single-molecule imaging, we show that Smc5/6 forms DNA loops by extrusion. Upon ATP hydrolysis, Smc5/6 reels DNA symmetrically into loops at a force-dependent rate of one kilobase pair per second. Smc5/6 extrudes loops in the form of dimers, whereas monomeric Smc5/6 unidirectionally translocates along DNA. We also find that the subunits Nse5 and Nse6 (Nse5/6) act as negative regulators of loop extrusion. Nse5/6 inhibits loop-extrusion initiation by hindering Smc5/6 dimeriza2023-01-01T00:00:00Z2023 Apr2025-04-22T10:05:09.582Z2025-04-05T23:23:23.026ZS-EPMC101329713707662610.1038/s41586-023-05963-3