Cited by 27Bacterial Genetics and BiotechnologyGenomics and Chromatin DynamicsDNA Repair Mechanisms

Loop-extruders alter bacterial chromosome topology to direct entropic forces for segregation

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Harju, Janni, van Teeseling, Muriel C. F., Broedersz, Chase P.·2024·Nature Communications

Abstract

Entropic forces have been argued to drive bacterial chromosome segregation during replication. In many bacterial species, however, specifically evolved mechanisms, such as loop-extruding SMC complexes and the ParAB S origin segregation system, contribute to or are even required for chromosome segregation, suggesting that entropic forces alone may be insufficient. The interplay between and the relative contributions of these segregation mechanisms remain unclear. Here, we develop a biophysical model showing that purely entropic forces actually inhibit bacterial chromosome segregation until late replication stages. By contrast, our model reveals that loop-extruders loaded at the origins of replication, as observed in many bacterial species, alter the effective topology of the chromosome, thereby redirecting and enhancing entropic forces to enable accurate chromosome segregation during replication. We confirm our model predictions with polymer simulations: purely entropic forces do not allow for concurrent replication and segregation, whereas entropic forces steered by specifically loaded loop-extruders lead to robust, global chromosome segregation during replication. Finally, we show how loop-extruders can complement locally acting origin separation mechanisms, such as the ParAB S system. Together, our results illustrate how changes in the geometry and topology of the polymer, induced by DNA-replication and loop-extrusion, impact the organization and segregation of bacterial chromosomes.

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  • Recent findings suggest that entropic forces may hinder, rather than promote, segregation in some contexts.

    “recent findings suggest that entropic forces may hinder, rather than promote, segregation in some contexts,81”

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Authors
Harju, J., van Teeseling, M. C. F., & Broedersz, C. P.
Affiliations
  • Vrije Universiteit Amsterdam (NL)
  • Center for NanoScience (DE)
Corresponding author
Broedersz, Chase P.
Venue
Nature Communications
Published
2024-05-30
Volume
15
Issue
1
Pages
4618-4618
ISSN
2041-1723 (ISSN-L)
OpenAlex
W4399169858
Cited by
27
References
79
Citations by year
2026: 5 · 2025: 13 · 2024: 9
FWCI
7.17
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • VU Research Portal (publishedVersion, other-oa)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • 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
Keywords
bacterial chromosome segregation, loop extrusion, entropic force, chromosome topology, SMC complex, ParABS system, DNA replication, biophysical model, polymer simulation, chromosome organization
MeSH terms
Bacterial Proteins, Chromosomes, Bacterial, DNA Replication, Escherichia coli, Replication Origin, Entropy, Chromosome Segregation

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