{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["McQuaid ME"],"funding":["Natural Sciences and Engineering Research Council of Canada","King Fahad Medical City","Canadian Institutes of Health Research"],"pagination":["e155648"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9215265"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["7(10)"],"pubmed_abstract":["The eukaryotic CDC45/MCM2-7/GINS (CMG) helicase unwinds the DNA double helix during DNA replication. The GINS subcomplex is required for helicase activity and is, therefore, essential for DNA replication and cell viability. Here, we report the identification of 7 individuals from 5 unrelated families presenting with a Meier-Gorlin syndrome-like (MGS-like) phenotype associated with hypomorphic variants of GINS3, a gene not previously associated with this syndrome. We found that MGS-associated GINS3 variants affecting aspartic acid 24 (D24) compromised cell proliferation and caused accumulation of cells in S phase. These variants shortened the protein half-life, altered key protein interactions at the replisome, and negatively influenced DNA replication fork progression. Yeast expressing MGS"],"journal":["JCI insight"],"pubmed_title":["Hypomorphic GINS3 variants alter DNA replication and cause Meier-Gorlin syndrome."],"pmcid":["PMC9215265"],"funding_grant_id":["RGPIN-2016-05559","PJT-159683","IRF 019-052"],"pubmed_authors":["Ahmed S","Dupuis L","Shago M","Al-Hassnan ZN","Khan ZU","Ahmed K","Dreseris ES","Kannu P","Wilson MD","Almanjomi F","Faqeih EA","Grover P","Stimec J","Campeau PM","Wurtele H","Boisvert FM","Yuki KE","Maddirevula S","Rousseau J","Maass PG","Campos EI","Tremblay R","Alkuraya FS","Kernohan KD","Tran S","McQuaid ME","Shaheen R","Grunebaum E","Boycott KM"],"additional_accession":[]},"is_claimable":false,"name":"Hypomorphic GINS3 variants alter DNA replication and cause Meier-Gorlin syndrome.","description":"The eukaryotic CDC45/MCM2-7/GINS (CMG) helicase unwinds the DNA double helix during DNA replication. The GINS subcomplex is required for helicase activity and is, therefore, essential for DNA replication and cell viability. Here, we report the identification of 7 individuals from 5 unrelated families presenting with a Meier-Gorlin syndrome-like (MGS-like) phenotype associated with hypomorphic variants of GINS3, a gene not previously associated with this syndrome. We found that MGS-associated GINS3 variants affecting aspartic acid 24 (D24) compromised cell proliferation and caused accumulation of cells in S phase. These variants shortened the protein half-life, altered key protein interactions at the replisome, and negatively influenced DNA replication fork progression. Yeast expressing MGS","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 May","modification":"2026-03-27T17:11:02.696Z","creation":"2025-04-22T03:08:50.776Z"},"accession":"S-EPMC9215265","cross_references":{"pubmed":["35603789"],"doi":["10.1172/jci.insight.155648"]}}