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The SMC Hinge is a Selective Gate for Obstacle Bypass

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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41467-025-65408-5

Authors

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Role:
Author
ORCID:
0000-0002-9498-6557
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Role:
Author
ORCID:
0000-0002-8390-2485
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Role:
Author
ORCID:
0000-0002-8881-3705
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Institution:
University of Oxford
Division:
MSD
Department:
Biochemistry
Sub department:
Biochemistry
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Biochemistry
Sub department:
Biochemistry
Role:
Author


Publisher:
Nature Research
Journal:
Nature Communications More from this journal
Volume:
16
Issue:
1
Article number:
10457
Publication date:
2025-11-25
Acceptance date:
2025-10-14
DOI:
EISSN:
2041-1723
ISSN:
2041-1723


Language:
English
Pubs id:
2337846
UUID:
uuid_1cf6bdf2-eb02-462c-aa32-01d118e3e589
Local pid:
pubs:2337846
Source identifiers:
3506434
Deposit date:
2025-11-25
ARK identifier:
This ORA record was generated from metadata provided by an external service. It has not been edited by the ORA Team.

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