Mutation

DNA: The Code of Life

Mutation

The Stability of DNA
Because of its double helix structure and general lack of reactivity, DNA is a relatively stable molecule. The most reactive part of DNA is its nitrogenous bases, but they are sheltered within the double helix and are partially neutralized through their hydrogen bonding. Mutations, or changes in the structure of DNA, can occur, though. Chemicals, heat, ultraviolet light, and radiation can all sometimes act as mutagens, potentially causing cancer or cell death. Though some mutations prove harmless or even beneficial, the vast majority are harmful. To guard itself against such damage, then, organisms have developed systems to protect themselves.

In many eukaryotes, ourselves included, DNA molecules are tightly wound around nucleosomes, spheres of the protein called histone. This positively charged protein forms an ionic bond with the negative backbone of DNA, and in the process shields the molecule.

DNA Repair
Despite a cell's best efforts, mutations sometimes occur. DNA, though, can usually be repaired thanks to one of its most crucial properties: it stores its information redundantly. For every strand of DNA there is a complementary strand, which may be used to double check information or provide a blueprint for reconstruction.

As DNA is replicated bases sometimes pair up incorrectly- a potential mutation. The enzyme DNA polymerase, however, has the ability to review a DNA strand to ensure that it is the perfect complement of its parent. This double-checking helps ensure the near perfect replication of DNA every time.

DNA polymerase also plays a role in another repair method- excision repair. During excision repair a portion of damaged DNA is excised, or cut out, and then rebuilt according to its complementary strand. DNA polymerase does the rebuilding while the enzyme ligase fuses the new section with the old strand. Because this process only involves the immediate area around the damage, transcription along the rest of the strand is left undisturbed.

It should be noted that damage is only considered a mutation if it is not repaired. If the mistake is eventually corrected, it is only considered a primary lesion. It is estimated that about 99.9% of primary lesions are fixed.

Point Mutations
A point mutations are minor changes in the DNA sequence. They are usually subtle and stand a good chance of being passed on to further generations. They come in three varieties:

Base Substitutions - one base is replaced by another. This is the most common mutation.

Insertion - a nitrogenous base is inserted into the DNA sequence.

Deletion - a nitrogenous base is deleted from the DNA sequence.

Base substitutions usually have the effect of changing the amino acid that a codon codes for, though this is not always the case. Because some codons are synonymous, these mutations sometimes have no effect. A change from GAA to GAG is one example- both code for glutamic acid. When the amino acid is changed, though, the protein that that gene creates may be quite different, causing harm to the organism. For example, if the sixth amino acid in human hemoglobin is changed from glutamic acid to valine through simple base substitution the change will cause sickle-cell anemia, a painful condition that eventually proves fatal.

Insertions and deletions are usually much more devastating to a cell than base substitutions because, unless they occur in a group of three bases, they will cause a reading-frame shift. In other words, if a base is added to a sequence all of the codons after the insertion will be shifted when they are transcribed. For example:
AGT GAC GGC AAT
becomes
TAG TGA CGG CAA T
if a T is added to the beginning. Needless to say, this will radically change the meaning of the information. Frame shift mutations are usually fatal to a cell.

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