For many years, cell biologists watched the puppet show of DNA synthesis, mitosis, and cytokinesis but had no idea of what lay behind the curtain controlling these events. It was not even clear whether there was a separate control system, or whether the processes of DNA synthesis, mitosis, and cytokinesis somehow controlled themselves. A major breakthrough came in the late 1980s with the identification of the key proteins of the control system, along with the realization that they are distinct from the proteins that perform the processes of DNA replication, chromosome segregation, and so on.
In this section, we first consider the basic principles upon which the cell-cycle control system operates. We then discuss the protein components of the system and how they work together to time and coordinate the events of the cell cycle.
The Cell-Cycle Control system Triggers the major Events of the Cell Cycle
The cell-cycle control system operates much like a timer that triggers the events of the cell cycle in a set sequence (Figure 17–9). In its simplest form—as seen in the stripped-down cell cycles of early animal embryos, for example—the control system is rigidly programmed to provide a fixed amount of time for the completion of each cell-cycle event. The control system in these early embryonic divisions is independent of the events it controls, so that its timing mechanisms continue to operate even if those events fail. In most cells, however, the control system does respond to information received back from the processes it controls. If some malfunction prevents the successful completion of DNA synthesis, for example, signals are sent to the control system to delay progression to M phase. Such delays provide time for the machinery to be repaired and also prevent the disaster that might result if the cycle progressed prematurely to the next stage—and segregated incompletely replicated chromosomes, for example.
The cell-cycle control system is based on a connected series of biochemical switches, each of which initiates a specific cell-cycle event. This system of switches possesses many important features that increase the accuracy and reliability of cell-cycle progression. First, the switches are generally binary (on/off ) and launch events in a complete, irreversible fashion. It would clearly be disastrous, for example, if events like chromosome condensation or nuclear-envelope breakdown were only partially initiated or started but not completed. Second, the cell-cycle control system is remarkably robust and reliable, partly because backup mechanisms and other features allow the system to operate effectively under a variety of conditions and even if some components fail. Finally, the control system is highly adaptable and can be modified to suit specific cell types or to respond to specific intracellular or extracellular signals.
number of cells 012 relative amount of DNA per cell
Figure 17–8 Analysis of DNA content with a flow cytometer. This graph shows typical results obtained for a proliferating cell population when the dna content of its individual cells is determined in a flow cytometer. (a flow cytometer, also called a fluorescence-activated cell sorter, or FaCs, can also be used to sort cells according to their fluorescence—see Figure 8–2). The cells analyzed here were stained with a dye that becomes fluorescent when it binds to dna, so that the amount of fluorescence is directly proportional to the amount of dna in each cell. The cells fall into three categories: those that have an unreplicated complement of dna and are therefore in g1, those that have a fully replicated complement of dna (twice the g1 dna content) and are in g2 or m phase, and those that have an intermediate amount of dna and are in s phase. The distribution of cells indicates that there are greater numbers of cells in g1 than in g2 + m phase, showing that g1 is longer than g2 + m in this population.
Are all chromosomes attached to the spindle?
Is all DNA replicated?
Is environment favorable?
G2 M S G1 CONTROLLER ENTER MITOSIS TRIGGER ANAPHASE AND PROCEED TO CYTOKINESIS ENTER CELL CYCLE AND PROCEED TO S PHASE START TRANSITION Is environment favorable? G2/M TRANSITION