Cited by 40Genomics and Chromatin DynamicsDNA Repair MechanismsDiffusion and Search Dynamics

SMC motor proteins extrude DNA asymmetrically and can switch directions

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Barth, Roman, Davidson, Iain F., van der Torre, Jaco, Taschner, Michael, Gruber, Stephan, Peters, Jan-Michael, Dekker, Cees·2025·Cell

Abstract

Structural maintenance of chromosomes (SMC) complexes organize the genome via DNA loop extrusion. Although some SMCs were reported to do so symmetrically, reeling DNA from both sides into the extruded DNA loop simultaneously, others perform loop extrusion asymmetrically toward one direction only. The mechanism underlying this variability remains unclear. Here, we examine the directionality of DNA loop extrusion by SMCs using in vitro single-molecule experiments. We find that cohesin and SMC5/6 do not reel in DNA from both sides, as reported before, but instead extrude DNA asymmetrically, although the direction can switch over time. Asymmetric DNA loop extrusion thus is the shared mechanism across all eukaryotic SMC complexes. For cohesin, direction switches strongly correlate with the turnover of the subunit NIPBL, during which DNA strand switching may occur. Apart from expanding by extrusion, loops frequently diffuse and shrink. The findings reveal that SMCs, surprisingly, can switch directions.

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  1. [61]61. Isiaka, B.N. ∙ Semple, J.I. ∙ Haemmerli, A. ... Cohesin forms fountains at active enhancers in C. elegans Preprint at bioRxiv. 2023; Crossref Scopus (0) Google Scholar

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Authors
Barth, R., Davidson, I. F., van der Torre, J., Taschner, M., Gruber, S., Peters, J.-M., & Dekker, C.
Affiliations
  • Delft University of Technology (NL)
  • Research Institute of Molecular Pathology (AT)
  • University of Lausanne (CH)
Corresponding author
Dekker, Cees
Venue
Cell
Publisher
Elsevier BV
Published
2025-02
Volume
188
Issue
3
Pages
749-763.e21
ISSN
0092-8674 (ISSN-L)
OpenAlex
W4406464901
Cited by
40
References
80
Citations by year
2026: 22 · 2025: 18
FWCI
12.02
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • IRIS (submittedVersion, cc-by-nc)
  • SERVAL (Université de Lausanne) (submittedVersion, cc-by-nc)
Funders
  • Human Frontier Science Program (RGP0057/2018)
  • Österreichische Forschungsförderungsgesellschaft (FFG-FO999902549)
  • Vienna Science and Technology Fund (LS19-029)
  • European Research Council
  • Medizinische Universität Wien
  • HORIZON EUROPE European Research Council (101020558, 883684, 724482)
  • Boehringer Ingelheim
  • European Commission
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Diffusion and Search Dynamics
Keywords
DNA loop extrusion, cohesin, genome organization, single-molecule DNA mechanics
MeSH terms
Cohesins, Chromosomal Proteins, Non-Histone, DNA, Saccharomyces cerevisiae, Cell Cycle Proteins, Saccharomyces cerevisiae Proteins

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