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PreprintCited by 1Genomics and Chromatin DynamicsDNA Repair MechanismsBacterial Genetics and Biotechnology

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Replisomes restrict SMC-mediated DNA-loop extrusion in vivo

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Liao, Qin, Brandão, Hugo B., Ren, Zhongqing, Wang, Xindan·2025·bioRxiv (Cold Spring Harbor Laboratory)
DOI 10.1101/2025.02.23.639750PMC PMC11870623
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Abstract

Structural maintenance of chromosomes (SMC) complexes organize genomes by extruding DNA loops, while replisomes duplicate entire chromosomes. These essential molecular machines must collide frequently in every cell cycle, yet how such collisions are resolved in vivo remains poorly understood. Taking advantage of the ability to load SMC complexes at defined sites in the Bacillus subtilis genome, we engineered head-on and head-to-tail collisions between SMC complexes and the replisome. Replisome progression was monitored by marker frequency analysis, and SMC translocation was monitored by time-resolved ChIP-seq and Hi-C. We found that SMC complexes do not impede replisome progression. By contrast, replisomes restrict SMC translocation regardless of collision orientations. Combining experimental data with simulations, we determined that SMC complexes are blocked by the replisome and then released from the chromosome. Occasionally, SMC complexes can bypass the replisome and continue translocating. Our findings establish that the replisome is a barrier to SMC-mediated DNA-loop extrusion in vivo , with implications for processes such as chromosome segregation, DNA repair, and gene regulation that require dynamic chromosome organization in all organisms.

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Metadata

Authors
Liao, Q., Brandão, H. B., Ren, Z., & Wang, X.
Affiliations
  • Indiana University Bloomington (US)
  • Illumina (United States) (US)
  • Memorial Sloan Kettering Cancer Center (US)
Corresponding author
Wang, Xindan
ORCID
Venue
bioRxiv (Cold Spring Harbor Laboratory)
Publisher
openRxiv
Published
2025-02-23
DOI
10.1101/2025.02.23.639750
PMC
PMC11870623
OpenAlex
W4407869821
Cited by
1
References
5
Citations by year
2026: 1
Type
posted content
Language
en
Open access
Licence
www.biorxiv.org/about/FAQ#license (vor)
Locations
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
Funders
  • National Institute of General Medical Sciences (R01GM143182, R01GM141242)
  • National Institute of Allergy and Infectious Diseases (R01AI172822)
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 › Genetics › Bacterial Genetics and Biotechnology
Keywords
SMC complex, replisome, DNA loop extrusion, chromosome organization, chromosome segregation, Bacillus subtilis

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