Cdt1 Phosphorylation by Cyclin A-dependent Kinases Negatively Regulates Its Function without Affecting Geminin Binding

摘要: The current concept regarding cell cycle regulation of DNA replication is that Cdt1, together with origin recognition complex and CDC6 proteins, constitutes the machinery loads minichromosome maintenance complex, a candidate replicative helicase, onto chromatin during G1 phase. actions are suppressed through phosphorylation by cyclin-dependent kinases (Cdks) after S phase to prohibit rereplication. It has been suggested in metazoan cells function Cdt1 blocked binding an inhibitor protein, geminin. However, functional relationship between Cdt1-geminin system Cdks remains be clarified. In this report, we demonstrate human phosphorylated cyclin A-dependent dependent on its cyclin-binding motif. Cdk resulted F-box protein Skp2 subsequent degradation. contrast, vitro activity was inhibited phosphorylation. geminin not affected Finally provide evidence inactivation Cdk1 results dephosphorylation rebinding murine FT210 synchronized around G2/M Taken together, these findings suggest also negatively regulated independent binding.