{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Cvetkovic MA"],"funding":["Cancer Research UK","European Research Council","Horizon 2020 Framework Programme","Medical Research Council","The Francis Crick Institute","Horizon 2020","Wellcome Trust","H2020 Marie Skłodowska-Curie Actions","Biotechnology and Biological Sciences Research Council"],"pagination":["4017-4031.e9"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7616792"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["83(22)"],"pubmed_abstract":["The MCM motor of the replicative helicase is loaded onto origin DNA as an inactive double hexamer before replication initiation. Recruitment of activators GINS and Cdc45 upon S-phase transition promotes the assembly of two active CMG helicases. Although work with yeast established the mechanism for origin activation, how CMG is formed in higher eukaryotes is poorly understood. Metazoan Downstream neighbor of Son (DONSON) has recently been shown to deliver GINS to MCM during CMG assembly. What impact this has on the MCM double hexamer is unknown. Here, we used cryoelectron microscopy (cryo-EM) on proteins isolated from replicating Xenopus egg extracts to identify a double CMG complex bridged by a DONSON dimer. We find that tethering elements mediating complex formation are essential for rep"],"journal":["Molecular cell"],"pubmed_title":["The structural mechanism of dimeric DONSON in replicative helicase activation."],"pmcid":["PMC7616792"],"funding_grant_id":["215510","845939","215510/Z/19/Z","MR/W001152/1","C17183/A23303","BB/T001860/1","CC1068","CC2009","820102","FC001065","23303"],"pubmed_authors":["Jhujh SS","Fernandez-Cuesta C","Gambus A","Costa A","Chauhan AS","Passaretti P","Skagia A","Reynolds-Winczura A","Stewart GS","Cvetkovic MA","Butryn A","Poovathumkadavil D","George R","Kingsley G"],"additional_accession":[]},"is_claimable":false,"name":"The structural mechanism of dimeric DONSON in replicative helicase activation.","description":"The MCM motor of the replicative helicase is loaded onto origin DNA as an inactive double hexamer before replication initiation. Recruitment of activators GINS and Cdc45 upon S-phase transition promotes the assembly of two active CMG helicases. Although work with yeast established the mechanism for origin activation, how CMG is formed in higher eukaryotes is poorly understood. Metazoan Downstream neighbor of Son (DONSON) has recently been shown to deliver GINS to MCM during CMG assembly. What impact this has on the MCM double hexamer is unknown. Here, we used cryoelectron microscopy (cryo-EM) on proteins isolated from replicating Xenopus egg extracts to identify a double CMG complex bridged by a DONSON dimer. We find that tethering elements mediating complex formation are essential for rep","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Nov","modification":"2026-07-09T12:12:58.3Z","creation":"2025-04-04T01:17:52.105Z"},"accession":"S-EPMC7616792","cross_references":{"pubmed":["37820732"],"doi":["10.1016/j.molcel.2023.09.029"]}}