{"doi":"10.7554/elife.79676","title":"The Nse5/6-like SIMC1-SLF2 complex localizes SMC5/6 to viral replication centers","abstract":"The human SMC5/6 complex is a conserved guardian of genome stability and an emerging component of antiviral responses. These disparate functions likely require distinct mechanisms of SMC5/6 regulation. In yeast, Smc5/6 is regulated by its Nse5/6 subunits, but such regulatory subunits for human SMC5/6 are poorly defined. Here, we identify a novel SMC5/6 subunit called SIMC1 that contains SUMO interacting motifs (SIMs) and an Nse5-like domain. We isolated SIMC1 from the proteomic environment of SMC5/6 within polyomavirus large T antigen (LT)-induced subnuclear compartments. SIMC1 uses its SIMs and Nse5-like domain to localize SMC5/6 to polyomavirus replication centers (PyVRCs) at SUMO-rich PML nuclear bodies. SIMC1's Nse5-like domain binds to the putative Nse6 orthologue SLF2 to form an anti-parallel helical dimer resembling the yeast Nse5/6 structure. SIMC1-SLF2 structure-based mutagenesis defines a conserved surface region containing the N-terminus of SIMC1's helical domain that regulates SMC5/6 localization to PyVRCs. Furthermore, SLF1, which recruits SMC5/6 to DNA lesions via its BRCT and ARD motifs, binds SLF2 analogously to SIMC1 and forms a separate Nse5/6-like complex. Thus, two Nse5/6-like complexes with distinct recruitment domains control human SMC5/6 localization.","journal":"eLife","year":2022,"id":248683,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":30,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":888189,"name":"Minghua Nie","orcid":"0000-0003-0222-7615","position":1,"is_corresponding":false},{"id":888190,"name":"Nicola Zilio","orcid":"0000-0003-0588-3917","position":2,"is_corresponding":false},{"id":233713,"name":"Shintaro Maeda","orcid":"0000-0002-8932-2051","position":3,"is_corresponding":false},{"id":344710,"name":"Yasaman Jami‐Alahmadi","orcid":"0000-0001-8289-2222","position":4,"is_corresponding":false},{"id":215684,"name":"Eros Lazzerini Denchi","orcid":"0000-0001-5378-4644","position":5,"is_corresponding":false},{"id":14958,"name":"James A. Wohlschlegel","orcid":"0000-0003-3399-901X","position":6,"is_corresponding":false},{"id":575783,"name":"Helle D. Ulrich","orcid":"0000-0003-0431-2223","position":7,"is_corresponding":false},{"id":233719,"name":"Takanori Otomo","orcid":"0000-0003-3589-238X","position":8,"is_corresponding":false},{"id":550220,"name":"Michael N. Boddy","orcid":"0000-0001-7618-4449","position":9,"is_corresponding":false},{"id":888188,"name":"Martina Oravcová","orcid":"0000-0001-6063-2227","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":null,"created_at":"2026-07-19T00:24:14.794521Z","pmid":"36373674","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":[]}