Genetics

The Consequences of Unrepaired Dna Damage



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Cells have evolved several ways to deal with damaged DNA, because it happens so often and can be so deadly. The first line of defense is DNA repair, but sometimes that fails. Next, the body tries to deal with DNA damage at the level of the cell. Cells with damage can be made to go quietly dormant while still holding their place in the body, or can be ordered to destroy themselves. If both these options fail, DNA damage can lead to birth defects or cancer.

Senescence

In general, cells lose their ability to divide, and thus reproduce, after about fifty divisions. This is called cellular senescence. However, if the DNA of cells becomes damaged, they may stop dividing far earlier.

Cells that are exposed to toxins or trauma that damages their DNA are hazardous. If they reproduce, they may spread their defects in ways that could be dangerous to the entire organism. Therefore, some cells are induced to enter senescence early. This is replicative senescence.

These cells still hold their place in the body, but do not divide. They are not dead or dying, and in fact are resistant to programmed cell death, or apoptosis.

Apoptosis

Apoptosis is cell suicide. It is also called programmed cell death, because it is a planned, orderly demise, which does minimum damage to surrounding cells. In essence, when a cell's DNA is damaged beyond repair, or when the cell's death is required for the whole body to work properly, the cell commits suicide. A child's brain development and a woman's menstruation both require apoptosis.

In apoptosis, the organism withdraws positive signals that induce the cells to live, and the cell receives negative signals that encourage the cell to die. Positive signals might be growth factors. Negative signals might include ionizing radiation, some kinds of chemotherapy, or a Tumor Necrosis Factor or other type of messenger molecule from the immune system. The messenger orders the cell to begin to die.

The cell may die in one of several ways. One pathway begins internally, when mitochondria, energy-producing organelles within cells, begin the destruction. Another pathway begins with an external signal that the cell should suicide. In both these cases, the cells cut up their own proteins, leaving debris, which is cleaned up by phagocytes, scavenger cells from the immune system.

Neural cells can die another way. Apoptosis inducing factor, already in the intermembrane space of the mitochondria, is released, and binds to and destroys the DNA of the cell, ultimately causing its death. Cells with very defective DNA are ordered to die because the alternatives are worse.

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Cancer

An immortal cell is a cancer cell, always growing. Therefore, to defend itself against cancer, the body denies immortality to most of its cells. Multiple sets of telomeres at the end of strands of DNA serve as counters for the number of times a cell has split. One set is stripped away with each cell division, until they are gone. Once they are gone, the cell can no longer reproduce.

Cancer cells have been damaged in a way that lets them evade this limit. They may be replacing their telomeres. The cells can grow into a mass that steals the body's resources for its own use, and swamps the body's defenses, a tumor.

Some chemotherapies target cells undergoing cell division. Cancer cells are vulnerable to such attacks, because they are dividing so often. Unfortunately, other cells that divide frequently are found in the intestines and the scalp, which is the reason for two of chemo's most notorious side effects: nausea and baldness. Some cancer therapies induce apoptosis in cancer cells, a very good thing.

About 80% of cancers occur after age fifty, perhaps because at that age the mechanisms for the repair of DNA are beginning to wear out. In very old age, DNA has been copied many times, and is likely to be full of errors. The immune system is also growing weaker, perhaps, making it less adept at sending cells into senescence or apoptosis.

Birth Defects

Birth defects can be another consequence of DNA that is not repaired. An unrepaired defect in the genes is called a mutation. A baby's DNA is the blueprint for many of his or her characteristics. The DNA is recombined from that of the parents, and thus the baby inherits the parent's traits. However, sometimes, the DNA is broken, and not repaired.

DNA is organized into 23 chromosome pairs in humans. If the chromosome number is wrong, or they are arranged incorrectly, birth defects can result. The commonest birth defect resulting from this kind of error is Downs Syndrome.

Sometimes a single defective gene in the entire array can cause a birth defect. Such defects include Huntington's disease. Huntington's is usually inherited from a parent with the disease, but can arise from disease-free parents through mutation.

Teratogens are substances that alter genes or their expression. Examples of teratogens include alcohol, certain viruses, and certain medicines and chemicals.

Conclusion

Even if the repair of DNA within a cell is unsuccessful, an organism still can defend itself with senescence and apoptosis. However, sometimes, unrepaired DNA causes cancer or birth defects. Some new therapies are being developed which use the mechanism of apoptosis to fight cancer.

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