{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yang R"],"funding":["NIH NIGMS","National Institutes of Health","NIH NCI"],"pagination":["111100"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12830165"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["302(2)"],"pubmed_abstract":["Meier-Gorlin syndrome (MGS) is a form of primordial dwarfism linked to mutations in DNA replication initiation factors. Many MGS variants affect proteins required for the first step of replication initiation-the licensing of replication origins-during which the origin recognition complex (ORC), CDC6, and CDT1 cooperatively load MCM2-7 complexes onto DNA as an MCM double hexamer. The specific impacts of MGS mutations on origin licensing remain poorly understood. In this study, we systematically analyze the effects of MGS-linked missense mutations in core domains of human origin licensing factors in a fully reconstituted in vitro MCM loading system. Our results show that MGS mutations inhibit origin licensing by blocking MCM recruitment or loading at discrete but distinct stages of the react"],"journal":["The Journal of biological chemistry"],"pubmed_title":["Molecular impacts of Meier-Gorlin syndrome mutations on human origin licensing."],"pmcid":["PMC12830165"],"funding_grant_id":["R35GM158287","R01-GM141313","F31-CA278331"],"pubmed_authors":["Hunker O","Bleichert F","Yang R","Kim J"],"additional_accession":[]},"is_claimable":false,"name":"Molecular impacts of Meier-Gorlin syndrome mutations on human origin licensing.","description":"Meier-Gorlin syndrome (MGS) is a form of primordial dwarfism linked to mutations in DNA replication initiation factors. Many MGS variants affect proteins required for the first step of replication initiation-the licensing of replication origins-during which the origin recognition complex (ORC), CDC6, and CDT1 cooperatively load MCM2-7 complexes onto DNA as an MCM double hexamer. The specific impacts of MGS mutations on origin licensing remain poorly understood. In this study, we systematically analyze the effects of MGS-linked missense mutations in core domains of human origin licensing factors in a fully reconstituted in vitro MCM loading system. Our results show that MGS mutations inhibit origin licensing by blocking MCM recruitment or loading at discrete but distinct stages of the react","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Dec","modification":"2026-06-13T05:14:45.993Z","creation":"2026-06-13T03:08:17.921Z"},"accession":"S-EPMC12830165","cross_references":{"pubmed":["41448435"],"doi":["10.1016/j.jbc.2025.111100"]}}