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Symmetry of loop extrusion by dimeric SMC complexes is DNA-tension-dependent

Pradhan, Biswajit ; Pinto, Adrian ; Kanno, Takaharu ; Tetiker, Damla ; Baaske, Martin D. ; Cutt, Erin ; Chatzicharlampous, Constantinos ; Schüler, Herwig LU orcid ; Deep, Amar and Corbett, Kevin D , et al. (2024) In bioRxiv : the preprint server for biology
Abstract

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... (More)

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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publishing date
type
Working paper/Preprint
publication status
published
subject
in
bioRxiv : the preprint server for biology
pages
26 pages
publisher
bioRxiv
external identifiers
  • pmid:39314301
ISSN
2692-8205
DOI
10.1101/2024.09.12.612694
language
English
LU publication?
yes
id
dbe2a7d7-d8f0-4302-a930-849dd26d62d5
date added to LUP
2024-11-21 18:08:34
date last changed
2025-04-04 14:24:44
@misc{dbe2a7d7-d8f0-4302-a930-849dd26d62d5,
  abstract     = {{<p>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 (&lt; 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.</p>}},
  author       = {{Pradhan, Biswajit and Pinto, Adrian and Kanno, Takaharu and Tetiker, Damla and Baaske, Martin D. and Cutt, Erin and Chatzicharlampous, Constantinos and Schüler, Herwig and Deep, Amar and Corbett, Kevin D and Aragon, Luis and Virnau, Peter and Björkegren, Camilla and Kim, Eugene}},
  issn         = {{2692-8205}},
  language     = {{eng}},
  month        = {{09}},
  note         = {{Preprint}},
  publisher    = {{bioRxiv}},
  series       = {{bioRxiv : the preprint server for biology}},
  title        = {{Symmetry of loop extrusion by dimeric SMC complexes is DNA-tension-dependent}},
  url          = {{http://dx.doi.org/10.1101/2024.09.12.612694}},
  doi          = {{10.1101/2024.09.12.612694}},
  year         = {{2024}},
}