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The Activating Kinases Cdk2 And Cdc7 In Oxygen Dependent Regulation Of Mammalian DNA Replication

Leenus Martin, Dinesh Anto Martin

In eukaryotes, the initiation of DNA replication is reversibly arrested by hypoxia at hypoxic pre-initiation state and which enters in to burst of initiation by reoxygenation. The hypoxic pre-initiation state appears similar to pre-replicative complex (pre-RC) in eukaryotes. The pre-RC is switched for replicon initiation by the activating kinases Cdk2 and Cdc7. In O2 dependent regulation of replicon initiation, Cdk2 activity is reported to be dispensable for the activation of hypoxic pre-initiation state by reoxygenation after several hours hypoxia. The phosphorylation of the second activating kinase Cdc7, the highest interaction with its substrate MCM2 and, the following phosphorylation and dissociation of MCM2 from the chromatin after reoxygenation of hypoxically suppressed replication provide a new pathway, which may be a possible pathway to release hypoxically arrested replicon initiation in course of reoxygenation.