The Smc5/6 complex is a DNA loop-extruding motor

Biswajit Pradhan, Takaharu Kanno, Miki Umeda Igarashi, Mun Siong Loke, Martin Dieter Baaske, Jan Siu Kei Wong, Kristian Jeppsson, Camilla Björkegren () and Eugene Kim ()
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Biswajit Pradhan: Max Planck Institute of Biophysics
Takaharu Kanno: Karolinska Institutet
Miki Umeda Igarashi: Karolinska Institutet
Mun Siong Loke: Max Planck Institute of Biophysics
Martin Dieter Baaske: Max Planck Institute of Biophysics
Jan Siu Kei Wong: Max Planck Institute of Biophysics
Kristian Jeppsson: Karolinska Institutet
Camilla Björkegren: Karolinska Institutet
Eugene Kim: Max Planck Institute of Biophysics

Nature, 2023, vol. 616, issue 7958, 843-848

Abstract: Abstract 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 dimerization but has no influence on ongoing loop extrusion. Our findings reveal functions of Smc5/6 at the molecular level and establish DNA loop extrusion as a conserved mechanism among eukaryotic SMC complexes.

Date: 2023
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DOI: 10.1038/s41586-023-05963-3

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