Molecular basis of cell division
The entry into S-phase or mitosis is subject of strict control through periodic activation of cell cycle regulators. Apart from internal controls, that ensure strict alteration of DNA replication and division, developmental factors control the number of cell divisions and timing of cell cycle progression. Cell cycle control varies between different developmental stages - G1 or G2 phase may be omitted, or even mitosis is skipped in enoreplicating cells. The key players driving DNA replication or entry into mitoses though are conserved.

Cyclin dependent kinases (cdk): Cyclin dependent kinases drive the cell into the next phase of the cell cycle, either S-phase or mitosis, by phosphorylating diverse target proteins. Different cdk proteins regulate different cell cycle phases. Although the concentration of cdks usually remains constant throughout the cell cycle, they are activated only at defined cell cycle phases. As their name suggests, they are associated with another type of molecules, the cyclins, which are required for cdk activation.

Cyclins: Cyclins act as subunits of the cyclin dependent kinases. In the prototype cell cycle, their concentration changes periodically over time – hence the name “cyclin”. Their concentration is regulated both transcriptionally and through periodic proteolysis.

Different combinations of cyclins and cyclin dependent kinases regulate the progression through different phases of the cell cycle. For example, cyclin A or cyclin B in complex with cdk1 (also called cdc2) are required for the entry into mitosis in Drosophila, whereas cyclin E together with cdk2 regulates the onset of DNA replication. Just as activation of the mitotic cdk1 through complexation with cyclinA and cyclinB promotes mitosis, destruction of the cyclins and thereby inactivation of the kinase is required for completion of mitosis. If the proteolytic degradation of cyclins is impaired, cells arrest in mitosis.

Kinases and phosphatases regulating cdks: In addition to their regulation by cyclins, the activity of cyclin dependent kinases is controlled through phosphorylation. In Drosophila, the string phosphatase removes inhibitory phosphates from the ATP binding site of cdk1.




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Cell division, molecules