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In low-mitogen, low-CDK environments, cells exit the cell cycle into a non-proliferative quiescent state, G0, that plays essential roles in stem cell maintenance and cellular homeostasis. CIZ1 regulates cell cycle and epigenetic programmes, and CIZ1 ablation promotes genomic instability after release from quiescence. Here, we show that CIZ1 contributes to mechanisms that temporally regulate cell cycle transitions in post-quiescent cells. CIZ1\u2212\/\u2212 (CIZ1 KO) fibroblasts re-entering the cell cycle from quiescence have reduced G1 phase and cell cycle length, mediated by increased intracellular CDK activity and early restriction point bypass via G1\/S cyclin overexpression. In addition,\u00a0CIZ1\u2212\/\u2212 cells are deficient in cyclin A chromatin binding and require increased CDK activity to initiate DNA replication, leading to DNA replication stress. Importantly, ectopic expression of CIZ1 or addition of recombinant CIZ1 reinstates the CDK threshold for initiation of DNA replication, reversing DNA replication stress and increasing replication fork rates. These data suggest that in post-quiescent cells, CIZ1 determines the threshold CDK activity required for the G1\/S transition to prevent DNA replication stress.<\/jats:p>","DOI":"10.1093\/nar\/gkag878","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:34:09Z","timestamp":1788521649000},"source":"Crossref","is-referenced-by-count":1,"title":["CIZ1 regulates G1 length and the CDK threshold for initiation of DNA replication to prevent DNA replication stress"],"prefix":"10.1093","volume":"54","author":[{"given":"James","family":"Tollitt","sequence":"first","affiliation":[{"name":"Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University , Bailrigg, Lancaster, LA1 4YQ ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus K","family":"Preedy","sequence":"additional","affiliation":[{"name":"Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University , Bailrigg, Lancaster, LA1 4YQ ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiernan","family":"Briggs","sequence":"additional","affiliation":[{"name":"Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University , Bailrigg, Lancaster, LA1 4YQ ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah L","family":"Allinson","sequence":"additional","affiliation":[{"name":"Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University , Bailrigg, Lancaster, LA1 4YQ ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0482-9954","authenticated-orcid":false,"given":"Christopher J","family":"Staples","sequence":"additional","affiliation":[{"name":"North West Cancer Research Institute, North Wales Medical School, Bangor University , Bangor, Gwynedd LL57 2UW ,","place":["United 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