17.3:

The Cell Cycle Control System

JoVE Core
分子生物学
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JoVE Core 分子生物学
The Cell Cycle Control System

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02:11 min

April 07, 2021

The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell division in the absence of a control mechanism leads to cancer and many genetic diseases.

To ensure DNA replication occurs correctly and each daughter cell inherits the right number of chromosomes, the cell has surveillance mechanisms that make up the cell cycle control system. There are at least two known cell cycle control methods. One of these processes includes a cascade of protein phosphorylations that transitions a cell from one phase to the next. Also, there is a series of checkpoints that monitor the completion of essential events and, if necessary, delay progression to the next phase. At every checkpoint, the regulator proteins prevent the cell initiation from entering the next phase until the previous phase's errors are rectified.

The first form of regulation includes a highly regulated family of kinases. Kinase activation requires interaction with a second subunit expressed at fixed points of the cell cycle. This secondary component is termed as- a phase-specific "cyclin"  that combines with its partner "cyclin-dependent kinase" (CDK), forming an active complex, each of which exhibits distinct substrate specificity. Regulatory phosphorylation and dephosphorylation fine-tune the function of cyclin-CDK complexes, ensuring a well-defined progression.

The second form of cell cycle regulation – checkpoint control, is more of a surveillance mechanism. Cell cycle checkpoints identify defects in crucial events such as DNA replication and chromosome segregation. For instance, DNA damage triggers a signaling cascade that activates several cell cycle inhibitors. These inhibitors bind critical cell cycle proteins to arrest the cycle until the risk of mutation has been eliminated.