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PreprintCited by 35DNA Repair MechanismsGenomics and Chromatin DynamicsMicrotubule and mitosis dynamics

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Cryo-EM structure of the Smc5/6 holo-complex

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Hallett, Stephen T., Harry, Isabella Campbell, Schellenberger, Pascale, Zhou, Lihong, Cronin, Nora B., Baxter, Jonathan, Etheridge, Thomas J., Murray, Johanne M., Oliver, Antony W.·2021·Nucleic Acids Research
DOI 10.1101/2021.11.25.470006PMC PMC9458440

Preprint — published as 10.1093/nar/gkac692 · Paper page

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Abstract

The Smc5/6 complex plays an essential role in the resolution of recombination intermediates formed during mitosis or meiosis, or as a result of the cellular response to replication stress. It also functions as a restriction factor preventing viral integration. Here, we report the cryo-EM structure of the six-subunit budding yeast Smc5/6 holo-complex, reconstituted from recombinant proteins expressed in insect cells – providing a full overview of the complex in its apo / non-liganded form, and revealing how the Nse1/3/4 subcomplex binds to the hetero-dimeric SMC protein core. In addition, we demonstrate that a region within the head domain of Smc5, equivalent to the ‘W-loop’ of Smc4 or ‘F-loop’ of Smc1, mediates an essential interaction with Nse1. Taken together, these data confirm a degree of functional equivalence between the structurally unrelated KITE and HAWK accessory subunits associated with SMC complexes.

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Metadata

Authors
Hallett, S. T., Harry, I. C., Schellenberger, P., Zhou, L., Cronin, N. B., Baxter, J., Etheridge, T. J., Murray, J. M., & Oliver, A. W.
Affiliations
  • University of Sussex (GB)
  • The Francis Crick Institute (GB)
Corresponding author
  • Etheridge, Thomas J.
  • Murray, Johanne M.
  • Oliver, Antony W.
ORCID
Venue
Nucleic Acids Research
Publisher
openRxiv
Published
2021-11-25
Volume
50
Issue
16
Pages
9505-9520
ISSN
0305-1048 (ISSN-L)
DOI
10.1101/2021.11.25.470006
PMC
PMC9458440
OpenAlex
W4292607806
Cited by
35
References
1
Citations by year
2026: 10 · 2025: 5 · 2024: 9 · 2023: 8 · 2022: 3
FWCI
2.04
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Nucleic Acids Research (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Sussex Research Online (University of Sussex) (submittedVersion, cc-by)
  • Figshare (submittedVersion, cc-by)
  • The Francis Crick Institute (cc-by)
Funders
  • Wellcome Trust (095605, 110047, /Z/15/Z, 110047/Z/15/Z, 095605/Z/11/A)
  • Cancer Research UK (C302/A24386, A24386)
  • University of Sussex
  • Medical Research Council (MR/PO18955/1, MR/P018955/1)
  • Biotechnology and Biological Sciences Research Council (BB/S001425/1)
Topics
  • 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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
Keywords
Smc5/6 complex, SMC complex, SMC5, SMC4, SMC1A, mitotic recombination, meiotic recombination, replication stress, viral replication restriction, Saccharomyces cerevisiae, protein complex structure
MeSH terms
Chromosomal Proteins, Non-Histone, Nuclear Proteins, Saccharomyces cerevisiae, Cell Cycle Proteins, Cryoelectron Microscopy, Saccharomyces cerevisiae Proteins

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