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Cited by 90Genomics and Chromatin DynamicsBacterial Genetics and BiotechnologyDNA Repair Mechanisms

DNA-loop-extruding SMC complexes can traverse one another in vivo

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Brandão, Hugo B., Ren, Zhongqing, Karaboja, Xheni, Mirny, Leonid A., Wang, Xindan·2021·Nature Structural & Molecular Biology
DOI 10.1038/s41594-021-00626-1PMC PMC8878250

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Abstract

Chromosome organization mediated by structural maintenance of chromosomes (SMC) complexes is vital in many organisms. SMC complexes act as motors that extrude DNA loops, but it remains unclear what happens when multiple complexes encounter one another on the same DNA in living cells and how these interactions may help to organize an active genome. We therefore created a crash-course track system to study SMC complex encounters in vivo by engineering defined SMC loading sites in the Bacillus subtilis chromosome. Chromosome conformation capture (Hi-C) analyses of over 20 engineered strains show an amazing variety of chromosome folding patterns. Through three-dimensional polymer simulations and theory, we determine that these patterns require SMC complexes to bypass each other in vivo, as recently seen in an in vitro study. We posit that the bypassing activity enables SMC complexes to avoid traffic jams while spatially organizing the genome.

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  • Hi-C data from B. subtilis are best reproduced by simulations in which SMCs can block each other and, in some cases, facilitate each other's unloading.

    “Hi-C data from B. subtilis are best reproduced by simulations in which SMCs can block each other and, in some cases, facilitate each other’s unloading.58”

    From Bringing the genetically minimal cell to life on a computer in 4D (2026) · cites this paper as [58]

    The Results section, “A model of SMC complexes bypassing each other explains experimental data” (page unavailable), reports that the best-matching model includes blocking and facilitated unloading. But it also requires SMCs to bypass one another; the Results section on polymer simulations says blocking and unloading without bypassing could not reproduce key Hi-C features. The claim omits that essential condition. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The authors made several simplifying assumptions about SMC behavior in the model that could be refined and complexified to better partition the chromosomes.

    “Although entropic segregation is one hypothesis, we made several simplifying assumptions about SMC behavior in our model that could be refined and complexified to better partition the chromosomes.58”

    From Bringing the genetically minimal cell to life on a computer in 4D (2026) · cites this paper as [58]

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Cited by

Sorted by citations

Authors
Brandão, H. B., Ren, Z., Karaboja, X., Mirny, L. A., & Wang, X.
Affiliations
  • Harvard University (US)
  • Indiana University Bloomington (US)
Corresponding author
  • Mirny, Leonid A.
  • Wang, Xindan
ORCID
Venue
Nature Structural & Molecular Biology
Publisher
Springer Science and Business Media LLC
Published
2021-07-26
Volume
28
Issue
8
Pages
642-651
ISSN
  • 1545-9985 (ISSN-L)
  • 1545-9993
DOI
10.1038/s41594-021-00626-1
PMC
PMC8878250
OpenAlex
W3184944554
Cited by
90
References
10
Citations by year
2026: 12 · 2025: 24 · 2024: 15 · 2023: 18 · 2022: 14 · 2021: 6 · 2020: 1
FWCI
4.16
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Structural & Molecular Biology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • Research Square (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (acceptedVersion)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion)
Funders
  • National Institutes of Health (DK 107980)
  • Natural Sciences and Engineering Research Council of Canada
  • National Cancer Institute (U01CA200147)
  • National Institute of General Medical Sciences (R01GM114190, R01GM141242)
  • National Institute of Diabetes and Digestive and Kidney Diseases (U54DK107980)
  • Common Fund
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Keywords
SMC complex, structural maintenance of chromosomes, DNA loop extrusion, chromosome organization, chromosome conformation, Hi-C, traffic congestion, Bacillus subtilis, chromosome folding
MeSH terms
Bacillus subtilis, Chromosomal Proteins, Non-Histone, DNA-Binding Proteins, DNA, Bacterial, Nucleic Acid Conformation, Genome, Bacterial, Cell Cycle Proteins, Multiprotein Complexes

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