The length of the cell cycle is highly variable even within the cells of an individual organism. In humans, the frequency of cell turnover ranges from a few hours in early embryonic development to an average of two to five days for epithelial cells, or to an entire human lifetime spent in G0 by specialized cells such as cortical neurons or cardiac muscle cells. There is also variation in the time that a cell spends in each phase of the cell cycle. When fast-dividing mammalian cells are grown in culture (outside the body under optimal growing conditions), the length of the cycle is approximately 24 hours. In rapidly dividing human cells with a 24-hour cell cycle, the G1 phase lasts approximately 11 hours. The timing of events in the cell cycle is controlled by mechanisms that are both internal and external to the cell.
Regulation at Internal Checkpoints
It is essential that daughter cells be exact duplicates of the parent cell. Mistakes in the duplication or distribution of the chromosomes lead to mutations that may be passed forward to every new cell produced from the abnormal cell. To prevent a compromised cell from continuing to divide, there are internal control mechanisms that operate at three main cell cycle checkpoints at which the cell cycle can be stopped until conditions are favorable. These checkpoints occur near the end of G1, at the G2–M transition, and during metaphase (Figure 6.7).
Figure 6.7 The cell cycle is controlled at three checkpoints. Integrity of the DNA is assessed at the G1 checkpoint. Proper chromosome duplication is assessed at the G2 checkpoint. Attachment of each kinetochore to a spindle fiber is assessed at the M checkpoint.
The G1 Checkpoint
The G1 checkpoint determines whether all conditions are favorable for cell division to proceed. The G1 checkpoint, also called the restriction point, is the point at which the cell irreversibly commits to the cell-division process. In addition to adequate reserves and cell size, there is a check for damage to the genomic DNA at the G1 checkpoint. A cell that does not meet all the requirements will not be released into the S phase.
The G2 Checkpoint
The G2 checkpoint bars the entry to the mitotic phase if certain conditions are not met. As in the G1checkpoint, cell size and protein reserves are assessed. However, the most important role of the G2checkpoint is to ensure that all of the chromosomes have been replicated and that the replicated DNA is not damaged.
The M Checkpoint
The M checkpoint occurs near the end of the metaphase stage of mitosis. The M checkpoint is also known as the spindle checkpoint because it determines if all the sister chromatids are correctly attached to the spindle microtubules. Because the separation of the sister chromatids during anaphase is an irreversible step, the cycle will not proceed until the kinetochores of each pair of sister chromatids are firmly anchored to spindle fibers arising from opposite poles of the cell.
The cell cycle is an orderly sequence of events. Cells on the path to cell division proceed through a series of precisely timed and carefully regulated stages. In eukaryotes, the cell cycle consists of a long preparatory period, called interphase. Interphase is divided into G1, S, and G2 phases. Mitosis consists of five stages: prophase, prometaphase, metaphase, anaphase, and telophase. Mitosis is usually accompanied by cytokinesis, during which the cytoplasmic components of the daughter cells are separated either by an actin ring (animal cells) or by cell plate formation (plant cells).
Each step of the cell cycle is monitored by internal controls called checkpoints. There are three major checkpoints in the cell cycle: one near the end of G1, a second at the G2–M transition, and the third during metaphase.
