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Human cohesin compacts DNA by loop extrusion

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Kim, Yoori, Shi, Zhubing, Zhang, Hongshan, Finkelstein, Ilya J., Yu, Hongtao·2019·Science

DOI 10.1126/science.aaz4475PMC PMC7387118

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Abstract

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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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
ORCID: Kim, Yoori
Shi, Zhubing
Zhang, Hongshan
Finkelstein, Ilya J.
Yu, Hongtao
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2019-12-13
Volume: 366
Issue: 6471
Pages: 1345-1349
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.aaz4475
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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Human cohesin compacts DNA by loop extrusion

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