{"doi":"10.17615/g6b7-ht67","title":"Concerted Loading of Mcm2–7 Double Hexamers around DNA during DNA Replication Origin Licensing","abstract":"The licensing of eukaryotic DNA replication origins, which ensures once per cell cycle replication, involves the loading of six related minichromosome maintenance proteins (Mcm2-7) into prereplicative complexes (pre-RCs). Mcm2-7 forms the core of the replicative DNA helicase, which is inactive in the pre-RC. The ATP-dependent Mcm2-7 loading reaction requires the Origin Recognition Complex (ORC), Cdc6 and Cdt1. We have reconstituted Mcm2-7 loading with purified budding yeast proteins. Using biochemical approaches and electron microscopy, we show that single heptamers of Cdt1·Mcm2-7 are loaded cooperatively into stable, head-to-head Mcm2-7 double hexamers connected via N-terminal rings. DNA runs through a central channel in the double hexamer, and, once loaded, Mcm2-7 can slide passively along double-stranded DNA. Our work has significant implications for understanding how eukaryotic DNA replication origins are chosen and licensed, how replisomes assemble during initiation and how unwinding occurs during DNA replication.","journal":"UNC Libraries","year":2020,"id":142531,"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":0.9522,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":247322,"name":"Edward P. Morris","orcid":"0000-0003-3544-0041","position":1,"is_corresponding":false},{"id":247320,"name":"Fabienne Beuron","orcid":"0000-0003-1513-6181","position":2,"is_corresponding":false},{"id":531466,"name":"Gökhan Tolun","orcid":"0000-0001-6166-9451","position":3,"is_corresponding":false},{"id":307697,"name":"Jack D. Griffith","orcid":"0000-0002-8357-8689","position":4,"is_corresponding":false},{"id":609024,"name":"John F.X. Diffley","orcid":"0000-0001-5184-7680","position":5,"is_corresponding":false},{"id":609023,"name":"Dirk Remus","orcid":"0000-0002-5155-181X","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:17:31.424593Z","pmid":null,"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":[]}