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bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.09.12.612694
preprint
1
Article
Symmetry of loop extrusion by dimeric SMC complexes is DNA-tension-dependent
Pradhan Biswajit http://orcid.org/0000-0002-6101-8728

Pinto Adrian
Kanno Takaharu
Tetiker Damla
Baaske Martin D.
Cutt Erin
Chatzicharlampous Constantinos
Schüler Herwig
Deep Amar
Corbett Kevin D.
Aragon Luis
Virnau Peter
Björkegren Camilla http://orcid.org/0000-0003-4059-3501

Kim Eugene http://orcid.org/0000-0002-1759-6360

12 9 2024
2024.09.12.612694https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.09.12.612694
nihpp-2024.09.12.612694.pdf
Structural maintenance of chromosome (SMC) complexes organize and regulate genomes via DNA loop extrusion. During this process, the complexes increase the loop size by reeling in DNA from one or both sides of the loop. The factors governing this symmetry remain unclear. Here, we combine single-molecule analysis and molecular dynamic simulations to investigate the symmetry of loop extrusion of various SMC complexes. We find that whereas monomeric condensin and cohesin are one-sided extruders, the symmetry of dimeric SMCs, such as Smc5/6 and Wadjet, is DNA tension dependent. At low DNA tension (< 0.1pN), Smc5/6 and Wadjet extrude DNA from both sides of the loop. At higher tension, however, they transition to a behavior akin to one-sided extruders, yet still capable of extruding from one or the other side thereby switching the direction of extrusion. Our simulations further reveal that thermal fluctuations significantly influence loop extrusion symmetry, causing variations in DNA reeling rates between the two motors in the dimeric complexes and their direction switching at stalling tensions. Our findings challenge the previous view of loop extrusion symmetry as a fixed characteristic, revealing its dynamic nature and regulation by both intrinsic protein properties and extrinsic factors.
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pmc
