Mitosis and Cell Division

Mitosis and Regulation of the Cell Cycle

Mitosis is a form of nuclear division in which replicated chromosomes are carefully organized and separated in preparation for cytoplasmic division; it is tightly regulated by cellular signals at a series of checkpoints that are controlled by the interaction of cyclin-dependent kinases and cyclins.

All organisms are made up of at least one cell. Cells provide support and structure for all living things, whether the cell is an entire single-celled bacterium, a leaf cell in a multicellular plant, or a skin cell in a cheetah. Cell division is the process by which one cell divides and becomes two new cells. When a cell divides, it is undergoing reproduction—making a copy of itself with identical genetic material. In multicellular organisms, cell division allows the growth of complex organisms, such as humans, from a single fertilized egg cell. Cell division continues throughout the lifetime of a multicellular organism, functioning in tissue growth, repair, maintenance, and reproduction. Cell division is a major component of the cell cycle, the life of a cell, from its formation to the time when it divides to produce a new cell.

Cell growth, cell division, and cell death are normal processes that happen regularly. In multicellular organisms, the cell cycle and cell division happen at different rates, depending on the type of cell. For example, human skin cells divide regularly throughout a person's life, whereas cells in the human heart divide only rarely, if at all. Regulation of cell division is thus of great importance to the proper function of an organism. Too much cell division can lead to unwanted growth, and too little cell division would fail to keep up with cell loss and lead to structural shrinkage. Mechanisms of cell growth regulation have been studied thoroughly, both to better understand the normal cell cycle and also to gain insight partially because of the connection of cell growth regulation with cancer.

The regulation of the cell cycle is maintained by the cell-cycle control system, a series of checkpoints directed by chemical signals in a cell that regulate growth and division. The cell cycle includes the G1, S, G2, and M phases. The major control checkpoints occur at different points in the cell cycle—near the end of the G1 phase, at the end of the G2 phase, and during the M phase. The gatekeepers of these checkpoints are regulatory molecules categorized into two types: cyclins and cyclin-dependent kinases. A cyclin-dependent kinase (Cdk) is a regulatory molecule (usually a protein) that functions as a gatekeeper, along with cyclins, to move a cell past checkpoints in the cell cycle. In general, Cdks are present at a stable concentration in a cell, regardless of which phase the cell is in. Most of the time Cdks are inactive. Cdks are tied to a specific cyclin, and the activity of Cdks is thus tied to the concentration of the cyclin partner. A cyclin is a regulatory molecule that functions as a gatekeeper, along with cyclase-dependent kinases (Cdks), to move a cell past checkpoints in the cell cycle. For example, the Cdk maturation-promoting factor (MPF) triggers the cell to enter the M phase when activated by its cyclin partner. Although MPF is present in a cell all the time, its activity is in direct response to the concentration of its cyclin.

In general, the cellular proteins involved in moving from one phase of the cell cycle to another are maintained in an inactive state until triggered by signals (usually proteins) produced inside and outside the cell. When internal and external signals increase the production of cyclins, they activate their corresponding Cdks through phosphorylation (adding phosphate groups, which are phosphorus atoms bound to four oxygen atoms). In turn, the Cdks activate a cascade of phosphorylation of cellular proteins that triggers the cell to move to the next phase of the cell cycle. The default inactive state provides the cell protection against unchecked growth and division. For example, muscle cells in the human heart never receive the signal to proceed through the G1 checkpoint to enter the division steps of the cell cycle. These cells exit the cell cycle and remain at rest (a phase called G0) for the duration of their lives. If the cell dies, it is replaced by cells coming from undifferentiated cells still in the cell cycle rather than from adjacent heart muscle cells. However, it is now known that some cells that have left the cell cycle can reenter it based on external signals, such as growth factors. This may happen in response to injury or other trauma. These signals override the default inactive states of the checkpoints and draw the cell back into the cell cycle.

Cell-Cycle Control System

MPF (maturation-promoting factor) activity, which triggers the cell to enter the M phase (mitosis), is tied to the relative concentration of its cyclin, a regulatory protein that varies in concentration levels. When the concentration of the cyclin exceeds a certain level, it triggers MPF activity.