{"doi":"10.1073/pnas.2026844118","title":"Integrative analysis reveals unique structural and functional features of the Smc5/6 complex","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.","journal":"Proceedings of the National Academy of Sciences","year":2021,"id":153706,"datarank":1.8420478376532643,"base_score":4.219507705176107,"endowment":4.219507705176107,"self_citation_contribution":0.6329261557764161,"citation_network_contribution":1.2091216818768482,"self_endowment_contribution":0.6329261557764161,"citer_contribution":1.2091216818768482,"corpus_percentile":null,"corpus_rank":null,"citation_count":67,"citer_count":57,"citers_with_citation_signal":43,"citers_with_endowment":43,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9504,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":651747,"name":"Shibai Li","orcid":"0000-0001-9293-6006","position":1,"is_corresponding":false},{"id":150452,"name":"Zheng Ser","orcid":"0000-0003-4297-7525","position":2,"is_corresponding":false},{"id":649827,"name":"Tanmoy Sanyal","orcid":"0000-0002-6009-9431","position":3,"is_corresponding":false},{"id":652660,"name":"Koyi Choi","orcid":null,"position":4,"is_corresponding":false},{"id":651748,"name":"Bingbing Wan","orcid":"0000-0001-8629-0616","position":5,"is_corresponding":false},{"id":651749,"name":"Huihui Kuang","orcid":"0000-0002-9891-1747","position":6,"is_corresponding":false},{"id":91660,"name":"Andrej Săli","orcid":"0000-0003-0435-6197","position":7,"is_corresponding":false},{"id":513174,"name":"Alex Kentsis","orcid":"0000-0002-8063-9191","position":8,"is_corresponding":false},{"id":252278,"name":"Dinshaw J. Patel","orcid":"0000-0002-9779-7778","position":9,"is_corresponding":false},{"id":63854,"name":"Xiaolan Zhao","orcid":"0000-0002-8302-6905","position":10,"is_corresponding":false},{"id":651746,"name":"You Yu","orcid":"0000-0002-2311-7477","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:43:44.759273Z","pmid":"33941673","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}