Cancer and the Cell Cycle

Evolution of cells has always been marked by two competing forces: the need for change, so the cell can evolve, and the need to stay the same, so daughter cells can inherit whatever genetic advantage the parent cell had. In the short term, cells work a very long day to make sure their daughter cells are as much like the original as possible. Cell cycle monitors, consisting of many different enzymes, check to make sure that everything is going well each time a cell divides, and if it is not, those monitors stop the cell from dividing until the problem is corrected. If the damage cannot be repaired, a protozoan remains stuck in midstream for the remainder of its life. If this happens to a cell in an animal's body, the cell is forced to commit suicide, in a process called apoptosis, by other cells in the immediate neighborhood or by the immune system.

G2 checkpoint Metaphase checkpoint

Stop if DNA replication Stop if all chromosomes was incomplete are not attached to the spindle

^ Gi checkpoint

Stop if the DNA is damaged

Cell cycle checkpoints. The cell cycle is equipped with three checkpoints to ensure that the daughter cells are identical and that there is no genetic damage. The circular arrow indicates the direction of the cycle.

The cell cycle consists of four stages or phases: cell division (M phase, for mitosis); a gap immediately after M phase, called G1; DNA synthesis (S phase); followed by another gap, called G2. The cycle includes three checkpoints: the first is a DNA damage checkpoint that occurs in G1. The monitors check for damage that may have occurred as a result of the last cell cycle or were caused by something in the environment, such as UV radiation or toxic chemicals. If damage is detected, DNA synthesis is blocked until it can be repaired. The second checkpoint occurs in G2, where the monitors make sure errors were not introduced when the chromosomes were duplicated during the S phase. The G1 and G2 checkpoints are sometimes referred to collectively as

DNA damage checkpoints. The third and final checkpoint occurs in M phase, to ensure that all of the chromosomes are properly attached to the spindle. This checkpoint is intended to prevent gross abnormalities in the daughter cells with regard to chromosome number. If a chromosome fails to attach to the spindle, one daughter cell will end up with too many chromosomes, while the other will have too few.

Typically, cancer cells lose one or more of their checkpoint monitors, so they divide whether things are right or not. This is the reason they develop an abnormal genome and physical appearance. Corrupting the genome in this way may seem to spell certain death for a cell, but it is really the means by which cancer cells reinvent themselves. The checkpoints are intended to maintain the status quo; without them the genetic profile of a cell, including which genes are on or off and which are mutated, can change very quickly and radically.

The T cells of our immune system can detect abnormal, potentially dangerous cells, and when they do they order those cells to commit suicide. The gross changes in a cancer cell's genetic structure, however, often knock out its ability to respond to those signals. When this happens, the cancer cell has gained immunity to apoptosis and is well on its way to fulfilling its quest for immortality and assuming the lifestyle enjoyed by its protozoan ancestors.

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