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The other 12 encode components of the CDC45\u2010MCM\u2010GINS helicase, around which the eukaryotic replisome forms, or are factors required for helicase assembly during DNA replication initiation. A role for DONSON in CDC45\u2010MCM\u2010GINS assembly was unanticipated, since DNA replication initiation can be reconstituted\n                    <jats:italic>in vitro<\/jats:italic>\n                    with purified proteins from budding yeast, which lacks DONSON. Using mouse embryonic stem cells as a model for the mammalian helicase, we show that DONSON binds directly but transiently to CDC45\u2010MCM\u2010GINS during S\u2010phase and is essential for chromosome duplication. Rapid depletion of DONSON leads to the disappearance of the CDC45\u2010MCM\u2010GINS helicase from S\u2010phase cells and our data indicate that DONSON is dispensable for loading of the MCM2\u20107 helicase core onto chromatin during G1\u2010phase, but instead is essential for CDC45\u2010MCM\u2010GINS assembly during S\u2010phase. These data identify DONSON as a missing link in our understanding of mammalian chromosome duplication and provide a molecular explanation for why mutations in human DONSON are associated with Meier\u2010Gorlin syndrome.\n                  <\/jats:p>","DOI":"10.15252\/embr.202357677","type":"journal-article","created":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T06:10:59Z","timestamp":1696227059000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["DONSON is required for CMG helicase assembly in the mammalian cell cycle"],"prefix":"10.1038","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5843-3704","authenticated-orcid":false,"given":"Cecile","family":"Evrin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3410-3369","authenticated-orcid":false,"given":"Vanesa","family":"Alvarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0880-9691","authenticated-orcid":false,"given":"Johanna","family":"Ainsworth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Fujisawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4424-9014","authenticated-orcid":false,"given":"Constance","family":"Alabert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8861-379X","authenticated-orcid":false,"given":"Karim PM","family":"Labib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,10,2]]},"reference":[{"key":"BFEMBR202357677_CR1","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/ncb2918","volume":"16","author":"C Alabert","year":"2014","unstructured":"Alabert C, Bukowski\u2010Wills JS, Lee SB, Kustatscher G, Nakamura K, de Lima AF, Menard P, Mejlvang J, Rappsilber J, Groth A (2014) Nascent chromatin capture proteomics determines chromatin dynamics during DNA replication and identifies unknown fork components. 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