The Cell Cycle and Apoptosis
The biological objective of every living organism is to grow and reproduce. Growth and reproduction are dependent on the proper regulation of the cell cycle in which the cell increases in size, doubles its genome and divides into two daughter cells each with a complete genome. The process of cell growth and division is called the cell cycle. The cell cycle is a normal process that occurs in all living organisms, but there are times when the cycle must end and the cells are programmed to die. This programmed death is called apoptosis.
The cell cycle has four distinct phases, Gap 1 (G1), Synthesis (S), Gap 2 (G2) which are collectively called Interphase, and the Mitosis (M) phase. Some cells do not divide. In these cases, the cells enter a G0 phase in which the cell cycle is suspended so it does not enter the S phase. Cells that will divide, must prepare for the division process prior to entering mitosis. Preparation for cell division occurs during interphase. Each of the three phases within interphase plays a specific role. During G1 the cell increases in size so that there is ample cellular material for the two daughter cells at the conclusion of mitosis. During this phase RNA is transcribed and translated but at not time is DNA synthesized. DNA replication begins at the start of the S phase. The DNA is replicated so that each daughter cell will receive a complete set of chromosomes. After DNA synthesis is complete, the cell enters the G2 phase. During G2 the cell continues to grow and make proteins. Once G2 is complete, the cell can enter the M phase or mitosis. At this point all cell growth and protein synthesis halts and resources are dedicated to the proper division of the cell.
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To ensure that the cells grows and divides properly it is regulated by tight controls. Control of the cell cycle is maintained by a system checks and balances at designated check points. The association of proteins is used to regulate the cell through the checkpoints. These proteins are called cyclins and cyclin dependent kinases (Cdk's). When associated, the cyclin/Cdk complex work to phosphorylate proteins required to move into the next phase of the cell cycle. There are three essential checkpoints within the cell cycle. The first checkpoint is START for yeasts or the G1 checkpoint in animal cells. At this point the G1 cyclin (cyclin D) binds to the Cdk-4 activating it. Once active the proteins required to move into the S phase are phosphorylated and the cell enters the synthesis phase. Once the cell enters the S phase, the G1 cyclin degrades. After synthesis is compete, the cell begins the G2 phase. A second checkpoint is located at the end of G2. At this point if all is well, a mitotic cyclin (cyclin B) binds to the M-phase Cdk to make an M-phase promoting factor. This promoting factor is phosphorylated and the cell enters mitosis. Shortly after metaphase of mitosis the mitotic cyclin degrades allowing mitosis to finish. |
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The cell cycle provides for new cells requires for growth and development as well as to replace those that have worn our or died. However, there are times when forcing a cell to die is required. Proper development may necessitate cell death, for example, the webbing that exists between the fingers and toes during fetal development are eliminated by apoptosis. Other conditions that initiate cell death by apoptosis are infection by a virus, cancer, damaged DNA and elimination of immune cells when they are not needed. In these situations the cell is instructed to commit suicide. The death process is systematic. Initially the cell shrinks followed by the formation of blister-like cell surface. Both the DNA and mitochondria are broken down. The cell breaks into small fragments which are consumed by macrophages.
Triggering apoptosis may occur by many different means depending on the reason for the cell death. Withdrawal of growth factors or treatment with glucocorticoids may initiate programmed cell death. Cancer can trigger cell death by activating t he p53 protein. Also, the immune system may attack target cells for apoptosis.
Regardless of the method of initiation, the process and function of apoptosis are the same.
Apoptosis is a necessary, orderly way to eliminate cells that are damaged, cancerous, or otherwise nonfunctional or eliminate cells that are no longer necessary for the proper development of the organism. Like the cell cycle, apoptosis is also tightly controlled to precent unwanted cell death.
References:
Apoptosis retrieved May 8, 2006:
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/A/Apoptosis.html
Cells Alive "The cell cycle" Retrieved on May 7, 2006 from http://www.cellsalive.com/cell_cycle.htm