Types of DNA Damage

Damage to DNA can result from several different types of processes. Hydrolysis, deamination, alkylation, and oxidation are all capable of causing a modification in one or more bases in a DNA sequence.

Hydrolysis. DNA consists of long strands of sugar molecules called deoxyri-bose that are linked together by phosphate groups. Each sugar molecule carries one of the four natural DNA bases: adenine, guanine, cytosine, or thymine (A, G, C, or T). The chemical bond between a DNA base and its respective deoxyribose, although relatively stable, is nonetheless subject to chance cleavage by a water molecule in a process known as spontaneous hydrolysis. Loss of the "purine" bases (guanine and adenine) is referred to as depurination, whereas loss of the "pyrimidine" bases (cytosine and thymine) is called depyrimidination. In mammalian cells, it is estimated that depurination occurs at the rate of about 10,000 purine bases lost per cell generation. The rate of depyrimidination is considerably slower, resulting in the loss of about 500 pyrimidine bases per cell generation.

The baseless sugars that result from these processes are commonly referred to as AP-sites (apurinic/apyrimidinic). They are potentially lethal to the cell, as they act to block the progress of DNA replication, but are efficiently repaired in a series of enzyme-catalyzed reactions collectively referred to as the base excision repair (BER) pathway. In fact, AP-sites are intentionally created during the course of BER.

Deamination. The bases that make up DNA are also vulnerable to modification of their chemical structure. One form of modification, called spontaneous deamination, is the loss of an amino group (-NH2). For example, cytosine (C), which is paired with guanine (G) in normal, double-stranded DNA, has an amino group attached to the fourth carbon (C4) of the base.

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