19.7 Surveillance Mechanisms in Cell Cycle Regulation

Surveillance mechanisms known as checkpoint pathways operate to ensure that the next cell cycle event is not initiated until the previous one has been completed. Checkpoint pathways consist of sensors that monitor a particular cellular event, a signaling cascade that initiates the response, and an effector that halts cell cycle progression and activates repair pathways when necessary. Cell cycle events monitored by checkpoint pathways include growth, DNA replication, DNA damage, kinetochore attachment to the mitotic spindle, and positioning of the spindle within the cell. These pathways are responsible for the extraordinarily high fidelity of cell division, ensuring that each daughter cell receives the correct number of accurately replicated chromosomes. They function by controlling the protein kinase activities of the cyclin-CDKs through a variety of mechanisms: regulation of the synthesis and degradation of cyclins, phosphorylation of CDKs at inhibitory sites, regulation of the synthesis and stability of CDK inhibitors (CKIs) that inactivate cyclin-CDK complexes, and regulation of the APC/C ubiquitin-protein ligase.

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