{"doi":"10.1016/j.jmb.2025.169492","title":"DNA Topoisomerase VI: Structure, Function and Mechanism","abstract":"• DNA topoisomerase VI, a type IIB topoisomerase originally found in archaea, has now been shown to occur in plants and bacteria, and possibly plasmodial parasites. • Topo VI is proposed to have a role in endoreplication in plants. • Structural and mechanistic studies show that topo VI conforms to a strand-passage mechanism, like the type IIA topoisomerases, but with key differences. • Some topo VI inhibitors are known but have yet to be exploited as chemotherapeutic agents. DNA topoisomerase VI (topo VI) is a type IIB topoisomerase that was originally found in archaea but later found in plants and some other eukaryotes and certain bacteria; claims that it is present in plasmodial parasites have yet to be substantiated. In plants it appears to have an essential role in endoreduplication, but its role in other organisms is less clear. Although topo VI is evolutionarily related to type IIA topoisomerases, it shows a different domain organisation and lacks an exit gate (C gate). Crystal structures of topo VI consolidate these distinctions and show protein cavities and subunit interfaces that are consistent with a double-strand passage mechanism. Single-molecule and ensemble measurements of topo VI reactions show that the rate of DNA relaxation is much slower than with its IIA counterparts, but that it shows a preference for decatenation over relaxation reactions. Radicicol, a known inhibitor of human topo II, also inhibits some topo VI enzymes, and recent drug screens have identified further compounds. Topo VI is ripe for exploitation as a target for herbicides and potentially for antibacterials.","journal":"Journal of Molecular Biology","year":2025,"id":578758,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9567,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":397462,"name":"Shannon J. McKie","orcid":"0000-0001-9364-796X","position":1,"is_corresponding":false},{"id":139653,"name":"Christian G. Noble","orcid":null,"position":2,"is_corresponding":false},{"id":397463,"name":"Anthony Maxwell","orcid":"0000-0002-5756-6430","position":3,"is_corresponding":false},{"id":907747,"name":"Adam M B Allen","orcid":null,"position":0,"is_corresponding":true}],"reference_count":99,"raw_metadata":null,"created_at":"2026-07-19T02:58:24.957414Z","pmid":"41135866","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":[]}