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http://purl.uniprot.org/citations/32669428http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/32669428http://www.w3.org/2000/01/rdf-schema#comment"DNA replication origins serve as sites of replicative helicase loading. In all eukaryotes, the six-subunit origin recognition complex (Orc1-6; ORC) recognizes the replication origin. During late M-phase of the cell-cycle, Cdc6 binds to ORC and the ORC-Cdc6 complex loads in a multistep reaction and, with the help of Cdt1, the core Mcm2-7 helicase onto DNA. A key intermediate is the ORC-Cdc6-Cdt1-Mcm2-7 (OCCM) complex in which DNA has been already inserted into the central channel of Mcm2-7. Until now, it has been unclear how the origin DNA is guided by ORC-Cdc6 and inserted into the Mcm2-7 hexamer. Here, we truncated the C-terminal winged-helix-domain (WHD) of Mcm6 to slow down the loading reaction, thereby capturing two loading intermediates prior to DNA insertion in budding yeast. In "semi-attached OCCM," the Mcm3 and Mcm7 WHDs latch onto ORC-Cdc6 while the main body of the Mcm2-7 hexamer is not connected. In "pre-insertion OCCM," the main body of Mcm2-7 docks onto ORC-Cdc6, and the origin DNA is bent and positioned adjacent to the open DNA entry gate, poised for insertion, at the Mcm2-Mcm5 interface. We used molecular simulations to reveal the dynamic transition from preloading conformers to the loaded conformers in which the loading of Mcm2-7 on DNA is complete and the DNA entry gate is fully closed. Our work provides multiple molecular insights into a key event of eukaryotic DNA replication."xsd:string
http://purl.uniprot.org/citations/32669428http://purl.org/dc/terms/identifier"doi:10.1073/pnas.2006231117"xsd:string
http://purl.uniprot.org/citations/32669428http://purl.uniprot.org/core/author"Li H."xsd:string
http://purl.uniprot.org/citations/32669428http://purl.uniprot.org/core/author"Schneider S."xsd:string
http://purl.uniprot.org/citations/32669428http://purl.uniprot.org/core/author"Yuan Z."xsd:string
http://purl.uniprot.org/citations/32669428http://purl.uniprot.org/core/author"Yan C."xsd:string
http://purl.uniprot.org/citations/32669428http://purl.uniprot.org/core/author"Stillman B."xsd:string
http://purl.uniprot.org/citations/32669428http://purl.uniprot.org/core/author"Bai L."xsd:string
http://purl.uniprot.org/citations/32669428http://purl.uniprot.org/core/author"Riera A."xsd:string
http://purl.uniprot.org/citations/32669428http://purl.uniprot.org/core/author"Speck C."xsd:string
http://purl.uniprot.org/citations/32669428http://purl.uniprot.org/core/author"Ivanov I."xsd:string
http://purl.uniprot.org/citations/32669428http://purl.uniprot.org/core/author"Dodd T."xsd:string
http://purl.uniprot.org/citations/32669428http://purl.uniprot.org/core/author"Magdalou I."xsd:string
http://purl.uniprot.org/citations/32669428http://purl.uniprot.org/core/date"2020"xsd:gYear
http://purl.uniprot.org/citations/32669428http://purl.uniprot.org/core/name"Proc Natl Acad Sci U S A"xsd:string
http://purl.uniprot.org/citations/32669428http://purl.uniprot.org/core/pages"17747-17756"xsd:string
http://purl.uniprot.org/citations/32669428http://purl.uniprot.org/core/title"Structural mechanism of helicase loading onto replication origin DNA by ORC-Cdc6."xsd:string
http://purl.uniprot.org/citations/32669428http://purl.uniprot.org/core/volume"117"xsd:string
http://purl.uniprot.org/citations/32669428http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/32669428
http://purl.uniprot.org/citations/32669428http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/32669428
http://purl.uniprot.org/uniprot/#_P29469-mappedCitation-32669428http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32669428
http://purl.uniprot.org/uniprot/#_P29496-mappedCitation-32669428http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32669428
http://purl.uniprot.org/uniprot/#_P24279-mappedCitation-32669428http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32669428
http://purl.uniprot.org/uniprot/#_P38132-mappedCitation-32669428http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32669428