CIZ1 regulates G1 length and the CDK threshold for initiation of DNA replication to prevent DNA replication stress
Year: 2026
Type: article
Abstract: Eukaryotic cell division is regulated by CDK activity that must reach critical CDK threshold levels to progress through cell cycle stages. 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 enhances 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-/- (CIZ1 KO) fibroblasts re-entering the cell cycle from quiescence have reduced G1 phase and cell cycle length, mediated increased intracellular CDK activity and early restriction point bypass via G1/S cyclin overexpression. In addition, CIZ1-/- 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-quiescence cells, CIZ1 determines the threshold CDK activity required for the G1/S transition to prevent DNA replication stress.
Source: Figshare
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7204204119