The SMC Hinge is a Selective Gate for Obstacle Bypass
Hon Wing Liu,
Florian Roisné-Hamelin,
Michael Taschner,
James Collier,
Madhusudhan Srinivasan and
Stephan Gruber ()
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Hon Wing Liu: University of Lausanne (UNIL), Department of Fundamental Microbiology (DMF), Faculty of Biology and Medicine (FBM)
Florian Roisné-Hamelin: University of Lausanne (UNIL), Department of Fundamental Microbiology (DMF), Faculty of Biology and Medicine (FBM)
Michael Taschner: University of Lausanne (UNIL), Department of Fundamental Microbiology (DMF), Faculty of Biology and Medicine (FBM)
James Collier: University of Oxford, Department of Biochemistry
Madhusudhan Srinivasan: University of Oxford, Department of Biochemistry
Stephan Gruber: University of Lausanne (UNIL), Department of Fundamental Microbiology (DMF), Faculty of Biology and Medicine (FBM)
Nature Communications, 2025, vol. 16, issue 1, 1-15
Abstract:
Abstract DNA loop-extruding SMC complexes play vital roles in genome maintenance and DNA immunity. However, how these ring-shaped DNA motors navigate large DNA-bound obstacles has remained unclear. Here, we demonstrate that a bacterial SMC Wadjet complex can efficiently bypass obstacles larger than the SMC coiled coil lumen when they are tethered to the extruded DNA by a single-stranded DNA or RNA linker. This bypass is mediated by the selective entrapment of the linker within the SMC hinge channel, which functions as an obligate gate—permitting passage of the linker while retaining double-stranded DNA stably inside the SMC ring and keeping associated obstacles outside. We further show that eukaryotic SMC hinges similarly accommodate ssDNA, and that the hinge is dispensable for loop extrusion by Wadjet, altogether suggesting that obstacle bypass represents the conserved, long-sought function of the SMC hinge toroid. By integrating hinge bypass with loop extrusion, we provide a mechanistic framework for how DNA-entrapping SMC complexes can generate chromosomal loops densely decorated with obstacles.
Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65408-5
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DOI: 10.1038/s41467-025-65408-5
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