Scientists identify a molecular machine that reshapes DNA inside cells
Researchers discovered that the Smc5/6 complex works like a motor to physically loop and reorganize DNA. The finding could unlock new ways to treat cancer, genetic disorders, and infections by targeting how cells manage their genetic material—opening doors for drug developers and biotech companies.
Originaltitel: The Smc5/6 complex is a DNA loop-extruding motor
Structural Maintenance of Chromosomes (SMC) protein complexes are essential for the spatial organization of chromosomes. While cohesin and condensin organize chromosomes by extruding DNA loops, the molecular functions of the third eukaryotic SMC complex, Smc5/6, remain largely unknown. Using single-molecule imaging, we reveal that Smc5/6 forms DNA loops by extrusion. Upon ATP-hydrolysis, Smc5/6 symmetrically reels DNA into loops at a force-dependent rate of 1 kilobase pairs per second. Smc5/6 extrudes loops in the form of a dimer, while monomeric Smc5/6 unidirectionally translocate along DNA. We also find that Nse5 and Nse6 (Nse5/6) subunits act as negative regulators of Smc5/6-mediated loop initiation and stability. Our findings reveal Smc5/6’s molecular functions, and establish loop extrusion as a conserved mechanism among eukaryotic SMC complexes. <h4>One-Sentence Summary</h4> Smc5/6 is a DNA-loop-extruding motor, establishing loop extrusion as a conserved mechanism among eukaryotic SMC complexes.