{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T05:19:27Z","timestamp":1788326367776,"version":"build-2803163510"},"reference-count":95,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hangzhou Natural Science Foundation","award":["2025SZRJJ0297"],"award-info":[{"award-number":["2025SZRJJ0297"]}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Issues Mol. Biol.","CIMB"],"abstract":"<jats:p>The Structural Maintenance of Chromosomes 5\/6 (SMC5\/6) complex is a key regulator of genome stability that participates in the recognition, stabilization, and processing of DNA intermediates generated during DNA replication and homologous recombination. Recent advances in structural and biochemical studies have revealed the architecture of the SMC5\/6 complex and elucidated the molecular mechanisms by which ATPase activity, DNA-binding modules, and SUMO-and ubiquitin-mediated regulatory pathways cooperate to maintain genome integrity. Extensive evidence has further demonstrated that SMC5\/6 functions as a broad-spectrum antiviral restriction factor by recognizing and silencing episomal viral genomes, whereas diverse viruses have evolved strategies to evade or counteract its activity. In addition, dysfunction of the SMC5\/6 complex has been associated with cancer, developmental disorders, and genome instability syndromes. This review summarizes recent advances in the structure, molecular mechanisms, antiviral functions, and disease relevance of the SMC5\/6 complex, providing a basis for a deeper understanding of its diverse biological functions and potential applications.<\/jats:p>","DOI":"10.3390\/cimb48090880","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:33:32Z","timestamp":1788262412000},"page":"880","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Multifunctional SMC5\/6 Complex in Genome Stability, Antiviral Restriction, and Human Disease"],"prefix":"10.3390","volume":"48","author":[{"given":"Yaqing","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Cardiology, the Second Affiliated Hospital, Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijie","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the Second Affiliated Hospital, Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310058, China"},{"name":"Edinburgh Medical School, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh EH8 9YL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiale","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the Second Affiliated Hospital, Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310058, China"},{"name":"Edinburgh Medical School, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh EH8 9YL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chubai","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the Second Affiliated Hospital, Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310058, China"},{"name":"Edinburgh Medical School, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh EH8 9YL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the Second Affiliated Hospital, Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310058, China"},{"name":"Edinburgh Medical School, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh EH8 9YL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the Second Affiliated Hospital, Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2311-7477","authenticated-orcid":false,"given":"You","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the Second Affiliated Hospital, Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310058, China"},{"name":"Edinburgh Medical School, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh EH8 9YL, UK"},{"name":"ZJE Cross Lung Research Alliance, International Joint Center for Biomedical Sciences, Zhejiang University, Haining 314400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1038\/nature08467","article-title":"The DNA-Damage Response in Human Biology and Disease","volume":"461","author":"Jackson","year":"2009","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1038\/s41580-023-00609-8","article-title":"Genome Control by SMC Complexes","volume":"24","author":"Hoencamp","year":"2023","journal-title":"Nat. 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