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Human cohesin compacts DNA by loop extrusion
Open accessAbstract
Cohesin is a chromosome-bound, multisubunit adenosine triphosphatase complex. After loading onto chromosomes, it generates loops to regulate chromosome functions. It has been suggested that cohesin organizes the genome through loop extrusion, but direct evidence is lacking. Here, we used single-molecule imaging to show that the recombinant human cohesin-NIPBL complex compacts both naked and nucleosome-bound DNA by extruding DNA loops. DNA compaction by cohesin requires adenosine triphosphate (ATP) hydrolysis and is force sensitive. This compaction is processive over tens of kilobases at an average rate of 0.5 kilobases per second. Compaction of double-tethered DNA suggests that a cohesin dimer extrudes DNA loops bidirectionally. Our results establish cohesin-NIPBL as an ATP-driven molecular machine capable of loop extrusion.
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“Loop extrusion was initially proposed theoretically based on molecular dynamics simulations [342, 435] and then validated in single-molecule assays [436, 437].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [437]
In the citing paper
“loop extrusion mediated by cohesin and CTCF mediates the formation of chromatin loops and self-interacting Topologically Associating Domains (TADs)”
From Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration (2023) · cites this paper as [83]
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Metadata
- Authors
- Kim, Y., Shi, Z., Zhang, H., Finkelstein, I. J., & Yu, H.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- The University of Texas at Austin (US)
- Corresponding author
- Kim, Yoori
- Shi, Zhubing
- Finkelstein, Ilya J.
- Yu, Hongtao
- Venue
- Science
- Published
- 2019-12-13
- Volume
- 366
- Issue
- 6471
- Pages
- 1345-1349
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC7387118
- OpenAlex
- W2989713781
- Cited by
- 701
- References
- 42
- Citations by year
- 2026: 84 · 2025: 88 · 2024: 84 · 2023: 106 · 2022: 99 · 2021: 132 · 2020: 105 · 2019: 3
- FWCI
- 28.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (GM120554, GM124096)
- Welch Foundation (I-1441, F-1808)
- Cancer Prevention and Research Institute of Texas (RP160667-P2)
- 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
- cohesin, NIPBL, loop extrusion, DNA condensation, chromosome organization, single-molecule imaging, ATP hydrolysis, force sensitivity, processivity
- MeSH terms
- Single Molecule Imaging, Cohesins, Chromosomal Proteins, Non-Histone, DNA, Proton-Translocating ATPases, Humans, Nucleic Acid Conformation, Nucleosomes, Cell Cycle Proteins, Protein Multimerization
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