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Journal Article

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

MPS-Authors
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Pradhan,  Biswajit       
Research Group Structure and Dynamics of Chromosomes, Max Planck Institute of Biophysics, Max Planck Society;

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Loke,  Mun Siong
Research Group Structure and Dynamics of Chromosomes, Max Planck Institute of Biophysics, Max Planck Society;

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Baaske,  Martin Dieter       
Research Group Structure and Dynamics of Chromosomes, Max Planck Institute of Biophysics, Max Planck Society;

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Wong,  Jan Siu Kei       
Research Group Structure and Dynamics of Chromosomes, Max Planck Institute of Biophysics, Max Planck Society;

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Kim,  Eugene       
Research Group Structure and Dynamics of Chromosomes, Max Planck Institute of Biophysics, Max Planck Society;

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s41586-023-05963-3-2.pdf
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Citation

Pradhan, B., Kanno, T., Umeda Igarashi, M., Loke, M. S., Baaske, M. D., Wong, J. S. K., et al. (2023). The Smc5/6 complex is a DNA loop-extruding motor. Nature, 616(7958), 843-848. doi:10.1038/s41586-023-05963-3.


Cite as: https://hdl.handle.net/21.11116/0000-000D-059A-0
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.