A hold-and-feed mechanism drives directional DNA loop extrusion by condensin
Open accessPublished version of a preprint
Abstract
Structural maintenance of chromosomes (SMC) protein complexes structure genomes by extruding DNA loops, but the molecular mechanism that underlies their activity has remained unknown. We show that the active condensin complex entraps the bases of a DNA loop transiently in two separate chambers. Single-molecule imaging and cryo–electron microscopy suggest a putative power-stroke movement at the first chamber that feeds DNA into the SMC–kleisin ring upon adenosine triphosphate binding, whereas the second chamber holds on upstream of the same DNA double helix. Unlocking the strict separation of “motor” and “anchor” chambers turns condensin from a one-sided into a bidirectional DNA loop extruder. We conclude that the orientation of two topologically bound DNA segments during the SMC reaction cycle determines the directionality of DNA loop extrusion.
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Cites
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BackgroundHuman cohesin compacts DNA by loop extrusion
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SMC motor proteins extrude DNA asymmetrically and can switch directions
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Structural basis for plasmid restriction by SMC JET nuclease
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What AlphaFold tells us about cohesin’s retention on and release from chromosomes
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- Authors
- Shaltiel, I. A., Datta, S., Lecomte, L., Hassler, M., Kschonsak, M., Bravo, S., Stober, C., Ormanns, J., Eustermann, S., & Haering, C. H.
- Affiliations
- Department of Biochemistry and Cell Biology, Julius Maximilian University of Würzburg, 97074 Würzburg, Germany.
- Heidelberg University (DE)
- University of Würzburg (DE)
- European Molecular Biology Laboratory (DE)
- Corresponding author
- Datta, Sumanjit
- Lecomte, Léa
- Eustermann, Sebastian
- Haering, Christian H.
- ORCID
- Venue
- Science
- Published
- 2022-06-03
- Volume
- 376
- Issue
- 6597
- Pages
- 1087-1094
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W4281793572
- Cited by
- 112
- References
- 7
- Citations by year
- 2026: 18 · 2025: 24 · 2024: 24 · 2023: 27 · 2022: 19
- FWCI
- 7.68
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Science (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Darwin Trust of Edinburgh
- H2020 European Research Council (681365)
- 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
- condensin, DNA loop extrusion, structural maintenance of chromosomes, power stroke, ATP binding, chromosome organization, single-molecule imaging, cryo-electron microscopy
- MeSH terms
- Single Molecule Imaging, Adenosine Triphosphatases, DNA, DNA-Binding Proteins, Nucleic Acid Conformation, Cryoelectron Microscopy, Multiprotein Complexes
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