In most eukaryotic cells, the cell-cycle control system governs cell-cycle progression at three major regulatory transitions (see Figure 17–9). The first is Start (or the restriction point) in late G1, where the cell commits to cell-cycle entry and chromosome duplication. The second is the G2/M transition, where the control system triggers the early mitotic events that lead to chromosome alignment on the mitotic spindle in metaphase. The third is the metaphase-to-anaphase transition, where the control system stimulates sister-chromatid separation, leading to the completion of mitosis and cytokinesis. The control system blocks progression through each of these transitions if it detects problems inside or outside the cell. If the control system senses problems in the completion of DNA replication, for example, it will hold the cell at the G2/M transition until those problems are solved. Similarly, if extracellular conditions are not appropriate for cell proliferation, the control system blocks progression through Start, thereby preventing cell division until conditions become favorable.
The Cell-Cycle Control system depends on Cyclically activated Cyclin-dependent protein kinases (Cdks)
Central components of the cell-cycle control system are members of a family of protein kinases known as cyclin-dependent kinases (Cdks). The activities of these kinases rise and fall as the cell progresses through the cycle, leading to cyclical changes in the phosphorylation of intracellular proteins that initiate or regulate the major events of the cell cycle. An increase in Cdk activity at the G2/M transition, for example, increases the phosphorylation of proteins that control chromosome condensation, nuclear-envelope breakdown, spindle assembly, and other events that occur in early mitosis.
Cyclical changes in Cdk activity are controlled by a complex array of enzymes and other proteins. The most important of these Cdk regulators are proteins known as cyclins. Cdks, as their name implies, are dependent on cyclins for their activity: unless they are bound tightly to a cyclin, they have no protein kinase activity (Figure 17–10). Cyclins were originally named because they undergo a cycle of synthesis and degradation in each cell cycle. The levels of the Cdk proteins, by contrast, are constant. Cyclical changes in cyclin protein levels result in the cyclic assembly and activation of cyclin–Cdk complexes at specific stages of the cell cycle.
Figure 17–9 The control of the cell cycle.
a cell-cycle control system triggers the essential processes of the cycle—such as dna replication, mitosis, and cytokinesis. The control system is represented here as a central arm—the controller—that rotates clockwise, triggering essential processes when it reaches specific transitions on the outer dial (yellow boxes). Information about the completion of cell-cycle events, as well as signals from the environment, can cause the control system to arrest the cycle at these transitions.
Figure 17–10 Two key components of the cell-cycle control system. When cyclin forms a complex with Cdk, the protein kinase is activated to trigger specific cell-cycle events. Without cyclin, Cdk is inactive.
There are four classes of cyclins, each defined by the stage of the cell cycle at which they bind Cdks and function. All eukaryotic cells require three of these classes (Figure 17–11): 1.
G1/S-cyclins activate Cdks in late G1 and thereby help trigger progression through Start, resulting in a commitment to cell-cycle entry. Their levels fall in S phase.
2.
S-cyclins bind Cdks soon after progression through Start and help stimulate chromosome duplication. S-cyclin levels remain elevated until mitosis, and these cyclins also contribute to the control of some early mitotic events.
3.
M-cyclins activate Cdks that stimulate entry into mitosis at the G2/M transition. M-cyclin levels fall in mid-mitosis. In most cells, a fourth class of cyclins, the G1-cyclins, helps govern the activities of the G1/S-cyclins, which control progression through Start in late G1.