CDT1 is a novel replication factor conserved throughout evolution, and it was first identified in S. pombe as a target of CDC10 transcriptional regulation. It has been demonstrated that CDT1 cooperates with CDC18/CDC6 in driving re-replication in G2 when the CDC18/CDC6 protein is overexpressed and that CDT1 depletion prevents the binding of MCM proteins to chromatin (1). Regulation of CDT1 plays a critical role in the licensing process. Inhibition of CDT1 activity occurs by multiple mechanisms, including ubiquitin-dependent proteolysis and binding to its potent inhibitor Geminin. Misregulation of the licensing process and defects in the ordered assembly and disassembly of the pre-RC alter the integrity of the genome. Thus, cell cycle regulation of CDT1 expression and function is responsible for licensing replication origins in G1 and preventing relicensing and hence rereplication in S phase.
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