ArticleProceedings of the National Academy of Sciences of the United States of America2021
Integrative analysis reveals unique structural and functional features of the Smc5/6 complex.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 62 citations in OpenAlex.
- Multi-subunit collaboration enables Smc5/6 to function as a composite SUMO E3 complex.Nature communications · 2026Article
- Smc5/6 uses its head-NSE module to preferentially associate with ssDNA gaps and ss-dsDNA junctions.Nucleic acids research · 2026Article
- Disruption of the structural maintenance of chromosomes 5/6 complex enables tumor mutagenesis.NAR cancer · 2026Article
- SMC complex unidirectionally translocates DNA by coupling segment capture with an asymmetric kleisin path.eLife · 2026Article
- Molecular determinants of Smc5/6 association with DNA junctions.Nature communications · 2026Article
- In-Cell Proteomics Enables High-Resolution Temporal Profiling of Cell Cycle Progression and DNA Damage Response in Saccharomyces cerevisiae.Proteomics · 2026Article
- Structural and mechanistic perspectives on Nse5/6 regulation of the Smc5/6 complex.Frontiers in molecular biosciences · 2026Review
- SMC5/6-mediated plasmid silencing is directed by SIMC1-SLF2 and antagonized by the SV40 large T antigen.eLife · 2025Article
- Tutorial on integrative spatiotemporal modeling by integrative modeling platform.Protein science : a publication of the Protein Society · 2025Article
- Frontiers in integrative structural modeling of macromolecular assemblies.QRB discovery · 2025Review
- Cryo-EM structures of Smc5/6 in multiple states reveal its assembly and functional mechanisms.Nature structural & molecular biology · 2024Article
- NSE5 subunit interacts with distant regions of the SMC arms in the Physcomitrium patens SMC5/6 complex.The Plant journal : for cell and molecular biology · 2024Article
- NFATC2IP is a mediator of SUMO-dependent genome integrity.Genes & development · 2024Article
- The SMC5/6 complex: folding chromosomes back into shape when genomes take a break.Nucleic acids research · 2024Review
- Article
- SMC5/6 Promotes Replication Fork Stability via Negative Regulation of the COP9 Signalosome.International journal of molecular sciences · 2024Article
- Article
- Molecular basis for Nse5-6 mediated regulation of Smc5/6 functions.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Large-scale phenogenomic analysis of human cancers uncovers frequent alterations affecting SMC5/6 complex components in breast cancer.NAR cancer · 2023Article
- The multi-functional Smc5/6 complex in genome protection and disease.Nature structural & molecular biology · 2023Review
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Structural maintenance of chromosomes (SMC) complexes are critical chromatin modulators. In eukaryotes, the cohesin and condensin SMC complexes organize chromatin, while the Smc5/6 complex directly regulates DNA replication and repair. The molecular basis for the distinct functions of Smc5/6 is poorly understood. Here, we report an integrative structural study of the budding yeast Smc5/6 holo-complex using electron microscopy, cross-linking mass spectrometry, and computational modeling. We show that the Smc5/6 complex possesses several unique features, while sharing some architectural characteristics with other SMC complexes. In contrast to arm-folded structures of cohesin and condensin, Smc5 and Smc6 arm regions do not fold back on themselves. Instead, these long filamentous regions interact with subunits uniquely acquired by the Smc5/6 complex, namely the Nse2 SUMO ligase and the Nse5/Nse6 subcomplex, with the latter also serving as a linchpin connecting distal parts of the complex. Our 3.0-Å resolution cryoelectron microscopy structure of the Nse5/Nse6 core further reveals a clasped-hand topology and a dimeric interface important for cell growth. Finally, we provide evidence that Nse5/Nse6 uses its SUMO-binding motifs to contribute to Nse2-mediated sumoylation. Collectively, our integrative study identifies distinct structural features of the Smc5/6 complex and functional cooperation among its coevolved unique subunits.
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