Human CDK2 inhibition modifies the dynamics of chromatin-bound minichromosome maintenance complex and replication protein A.

摘要: Minichromosome maintenance (MCM) proteins form a complex and possess helicase activity to unwind the DNA duplex establish replication fork. To assure that origins only fire once per cell cycle, MCM is removed from chromatin inactivated as cells exit S phase. In this report, we demonstrate CDK2 depletion in human leads an overall phosphorylation defect at mitosis with increased rereplication, correlated accumulation of chromatin-bound proteins. We show suppression results decreased MCM4 multiple serine threonine sites. addition, inhibition induces increase protein A (RPA) which should bind single-stranded regions, possibly establishing intermediate activates ATR cascade. Finally, observe loss function G1 delays initiation while it promotes rereplication G2/M. Thus, by modulating phospho-status regulating origin firing, phase appears be integrated component cellular machinery required for temporally controlling maintaining genomic stability.