ArticleProceedings of the National Academy of Sciences of the United States of America2022
Cryo-EM structure of DNA-bound Smc5/6 reveals DNA clamping enabled by multi-subunit conformational changes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Advances in the Application of Protein Language Modeling for Nucleic Acid Protein Binding Site Prediction.Genes · 2024Pooled it
- Submolecular video-imaging of the Smc5/6 complex topologically bound to DNA.Nature communications · 2026Article
- The Multifunctional SMC5/6 Complex in Genome Stability, Antiviral Restriction, and Human Disease.Current issues in molecular biology · 2026Review
- Structural and functional insights into HBx-Smc6 targeting for HBV inhibition.Cell research · 2026Article
- 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
- Protein-nucleic acid binding site prediction using interpretable Kolmogorov-Arnold networks with hypergraph representation learning.Bioinformatics (Oxford, England) · 2026Article
- Disruption of the structural maintenance of chromosomes 5/6 complex enables tumor mutagenesis.NAR cancer · 2026Article
- Allelic Analysis ofInternational journal of molecular sciences · 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
- DNA actively regulates the "safety-belt" dynamics of condensin during loop extrusion.Nature communications · 2026Article
- Structural basis for Lamassu-based antiviral immunity and its evolution from DNA repair machinery.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Separation-of-Function Alleles ofBiomolecules · 2025Article
- Filling in missing puzzle pieces in protein structural biology with cross-linking mass spectrometry.QRB discovery · 2025Review
- All eukaryotic SMC proteins induce a twist of -0.6 at each DNA loop extrusion step.Science advances · 2024Article
- Cryo-EM structures of Smc5/6 in multiple states reveal its assembly and functional mechanisms.Nature structural & molecular biology · 2024Article
- The SMC5/6 complex prevents genotoxicity upon APOBEC3A-mediated replication stress.The EMBO journal · 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
- Crucial role of the NSE1 RING domain in Smc5/6 stability and FANCM-independent fork progression.Cellular and molecular life sciences : CMLS · 2024Article
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8 authors.
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Abstract
Structural maintenance of chromosomes (SMC) complexes are essential for chromatin organization and functions throughout the cell cycle. The cohesin and condensin SMCs fold and tether DNA, while Smc5/6 directly promotes DNA replication and repair. The functions of SMCs rely on their abilities to engage DNA, but how Smc5/6 binds and translocates on DNA remains largely unknown. Here, we present a 3.8 Å cryogenic electron microscopy (cryo-EM) structure of DNA-bound Saccharomyces cerevisiae Smc5/6 complex containing five of its core subunits, including Smc5, Smc6, and the Nse1-3-4 subcomplex. Intricate interactions among these subunits support the formation of a clamp that encircles the DNA double helix. The positively charged inner surface of the clamp contacts DNA in a nonsequence-specific manner involving numerous DNA binding residues from four subunits. The DNA duplex is held up by Smc5 and 6 head regions and positioned between their coiled-coil arm regions, reflecting an engaged-head and open-arm configuration. The Nse3 subunit secures the DNA from above, while the hook-shaped Nse4 kleisin forms a scaffold connecting DNA and all other subunits. The Smc5/6 DNA clamp shares similarities with DNA-clamps formed by other SMCs but also exhibits differences that reflect its unique functions. Mapping cross-linking mass spectrometry data derived from DNA-free Smc5/6 to the DNA-bound Smc5/6 structure identifies multi-subunit conformational changes that enable DNA capture. Finally, mutational data from cells reveal distinct DNA binding contributions from each subunit to Smc5/6 chromatin association and cell fitness. In summary, our integrative study illuminates how a unique SMC complex engages DNA in supporting genome regulation.
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