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Regulation of the Cell Cycle
The cell cycle is controlled by a cyclically operating set of reaction sequences that both trigger and coordinate key events in the cell cycle
The cell-cycle control system is driven by a built-in clock that can be adjusted by external stimuli (chemical messages)
Checkpoint - a critical control point in the cell cycle where stop and go-ahead signals can regulate the cell cycle
Animal cells have built-in stop signals that halt the cell cycles and checkpoints until overridden by go-ahead signals.
Three Major checkpoints are found in the G1, G2, and M phases of the cell cycle
The G1 checkpoint - the Restriction Point
The G1 checkpoint ensures that the cell is large enough to divide, and that enough nutrients are available to support the resulting daughter cells.
If a cell receives a go-ahead signal at the G1 checkpoint, it will usually continue with the cell cycle
If the cell does not receive the go-ahead signal, it will exit the cell cycle and switch to a non-dividing state called G0
Actually, most cells in the human body are in the G0 phase
The G2 checkpoint ensures that DNA replication in S phase has been completed successfully.
The metaphase checkpoint ensures that all of the chromosomes are attached to the mitotic spindle by a kinetochore.
Cyclins and Cyclin-Dependent Kinases - The Cell-Cycle Clock
Rhythmic fluctuations in the abundance and activity of cell-cycle control molecules pace the events of the cell cycle.
Kinase - a protein which activates or deactivates another protein by phosphorylating them.
Kinases give the go-ahead signals at the G1 and G2 checkpoints
The kinases that drive these checkpoints must themselves be activated
The activating molecule is a cyclin, a protein that derives its name from its cyclically fluctuating concentration in the cell
Because of this requirement, these kinases are called cyclin-dependent kinases, or Cdk's
MPF - Maturation Promoting Factor (M-phase promoting factor)
Cyclins accumulate during the G1, S, and G2 phases of the cell cycle
By the G2 checkpoint, enough cyclin is available to form MPF complexes (aggregations of Cdk and cyclin) which initiate mitosis
MPF apparently functions by phosphorylating key proteins in the mitotic sequence
Later in mitosis, MPF switches itself off by initiating a process which leads to the destruction of cyclin
Cdk, the non-cyclin part of MPF, persists in the cell as an inactive form until it associates with new cyclin molecules synthesized during interphase of the next round of the cell cycle
PDGF - Platelet-Derived Growth Factors - An Example of an External Signal for Cell Division
PDGF is required for the division of fibroblasts which are essential in wound healing
When injury occurs, platelets (blood cells important in blood clotting) release PDGF
Fibroblasts are a connective tissue cells which possess PDGF receptors on their plasma membranes
The binding of PDGF activates a signal-transduction pathway that leads to a proliferation of fibroblasts and a healing of the wound
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