{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:59:08Z","timestamp":1787018348717,"version":"build-2736575974"},"reference-count":70,"publisher":"American Society for Clinical Investigation","issue":"10","license":[{"start":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T00:00:00Z","timestamp":1660694400000},"content-version":"vor","delay-in-days":86,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"crossref","award":["RGPIN-2016-05559"],"award-info":[{"award-number":["RGPIN-2016-05559"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["PJT-159683"],"award-info":[{"award-number":["PJT-159683"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100011680","name":"King Fahad Medical City","doi-asserted-by":"crossref","award":["IRF 019-052"],"award-info":[{"award-number":["IRF 019-052"]}],"id":[{"id":"10.13039\/501100011680","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,23]]},"abstract":"<jats:p>\n                    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\u2013like (MGS-like) phenotype associated with hypomorphic variants of\n                    <jats:italic>GINS3<\/jats:italic>\n                    , a gene not previously associated with this syndrome. We found that MGS-associated\n                    <jats:italic>GINS3<\/jats:italic>\n                    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-associated variants of\n                    <jats:italic>PSF3<\/jats:italic>\n                    (the yeast\n                    <jats:italic>GINS3<\/jats:italic>\n                    ortholog) also displayed impaired growth, S phase progression defects, and decreased Psf3 protein stability. We further showed that mouse embryos homozygous for a D24 variant presented intrauterine growth retardation and did not survive to birth, and that fibroblasts derived from these embryos displayed accelerated cellular senescence. Taken together, our findings implicate\n                    <jats:italic>GINS3<\/jats:italic>\n                    in the pathogenesis of MGS and support the notion that hypomorphic variants identified in this gene impaired cell and organismal growth by compromising DNA replication.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.155648","type":"journal-article","created":{"date-parts":[[2022,5,22]],"date-time":"2022-05-22T14:00:55Z","timestamp":1653228055000},"source":"Crossref","is-referenced-by-count":22,"title":["Hypomorphic GINS3 variants alter DNA replication and cause Meier-Gorlin syndrome"],"prefix":"10.1172","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0491-127X","authenticated-orcid":true,"given":"Mary E.","family":"McQuaid","sequence":"first","affiliation":[{"name":"Maisonneuve-Rosemont Hospital Research Center, Montreal, Quebec, 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