Cited by 34Bacterial Genetics and BiotechnologyDNA Repair MechanismsGenomics and Chromatin Dynamics

Structural basis for plasmid restriction by SMC JET nuclease

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Roisné-Hamelin, Florian, Liu, Hon Wing, Taschner, Michael, Li, Yan, Gruber, Stephan·2024·Molecular Cell

Published version of a preprint

Abstract

DNA loop-extruding SMC complexes play crucial roles in chromosome folding and DNA immunity. Prokaryotic SMC Wadjet (JET) complexes limit the spread of plasmids through DNA cleavage, yet the mechanisms for plasmid recognition are unresolved. We show that artificial DNA circularization renders linear DNA susceptible to JET nuclease cleavage. Unlike free DNA, JET cleaves immobilized plasmid DNA at a specific site, the plasmid-anchoring point, showing that the anchor hinders DNA extrusion but not DNA cleavage. Structures of plasmid-bound JetABC reveal two presumably stalled SMC motor units that are drastically rearranged from the resting state, together entrapping a U-shaped DNA segment, which is further converted to kinked V-shaped cleavage substrate by JetD nuclease binding. Our findings uncover mechanical bending of residual unextruded DNA as molecular signature for plasmid recognition and non-self DNA elimination. We moreover elucidate key elements of SMC loop extrusion, including the motor direction and the structure of a DNA-holding state.

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Crossref · 10.1016/j.molcel.2024.01.009

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Authors
Roisné-Hamelin, F., Liu, H. W., Taschner, M., Li, Y., & Gruber, S.
Affiliations
University of Lausanne (CH)
Corresponding author
Gruber, Stephan
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2024-03
Volume
84
Issue
5
Pages
883-896.e7
ISSN
1097-2765 (ISSN-L)
OpenAlex
W4391486282
Cited by
34
References
74
Citations by year
2026: 6 · 2025: 20 · 2024: 8
FWCI
9.06
Type
journal article
Language
en
Open access
Locations
  • Molecular Cell (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • IRIS (submittedVersion)
  • SERVAL (Université de Lausanne) (submittedVersion)
Funders
  • European Research Council (724482)
  • European Molecular Biology Organization (ATLF 302-2022, ALTF 490-2021, E248A)
  • Université de Genève
  • École Polytechnique Fédérale de Lausanne
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
loop extrusion, DNA circularization, DNA kinking, DNA bending, chromosome folding
MeSH terms
DNA, Endonucleases, Plasmids, Prokaryotic Cells, Cell Cycle Proteins

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