Deoxyribonucleic Acid can be damaged by a number of agents, which include oxygen, water, naturally occurring chemicals in our diet, and radiation. Because damage to DNA can change the sequence of bases, a cell must be able to repair alterations in the DNA code if it is to survive and pass on the DNA database unaltered to its progeny cells.
The most common damage suffered by a DNA molecule is depurination—the loss of an adenine or guanine because the bond between the purine base and the deoxyribose sugar to which it is attached is hydrolyzed by water (Fig. 5.3). Within each human cell about 5000-10,000 depurinations occur every day.
Deamination is a less frequent event; it happens about 100 times a day in every human cell. Collision of water molecules with the bond linking the amine group to cy-tosine sets off a spontaneous deamination that produces uracil (Fig. 5.3). Cytosine base pairs with guanine, whereas uracil pairs with adenine. If this change were not corrected, then a CG base pair would mutate to a UA base pair the next time the DNA strand was replicated.
Ultraviolet light or chemical carcinogens such as benzopyrene, found in cigarette smoke, can also disrupt the structure of DNA. The absorption of ultraviolet light can cause two adjacent thymine residues to link and form a thymine dimer (Fig. 5.4). If uncorrected, thymine dimers create a distortion in the DNA helix known as a bulky lesion. This inhibits normal base pairing between the two strands of the double helix and blocks the replication process. Ultraviolet light has a powerful germicidal action and is widely used to sterilize equipment. One of the reasons why bacteria are killed by this treatment is because the formation of large numbers of thymine dimers prevents replication.
If there were no way to correct altered DNA, the rate of mutation would be intolerable. DNA excision and DNA repair enzymes have evolved to detect and to repair altered DNA. The role of the repair enzymes is to cut out (excise) the damaged portion of DNA and then to repair the base sequence. Much of our knowledge on DNA repair has been derived from studies on E. coli, but the general principles apply to other organisms such as ourselves. Repair is possible because DNA comprises two complementary strands. If the repair mechanisms can identify which of the two strands is the damaged one, it can then be repaired as good as new by rebuilding it to be complementary to the undamaged one.
Two types of excision repair are described in this section: base excision repair and nucleotide excision repair. The common themes of each of these repair mechanisms are: (1) An enzyme recognizes the damaged DNA, (2) the damaged portion is removed, (3) DNA polymerase inserts the correct nucleotide(s) into position (according to the base sequence of the second DNA strand), and (4) DNA ligase joins the newly repaired section to the remainder of the DNA strand.
Base excision-repair is needed to repair DNAs that have lost a purine (depurination), or where a cytosine has been deaminated to uracil (U). Although uracil is a normal constituent of RNA, it does not form part of undamaged DNA and is recognized and removed by the depurination
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