FIGURE 13.20 Inversion of DNA by Mispairing of Inverted Repeats
The DNA molecule shown has two copies of a sequence that are inverted relative to each other. Three intervening genes (Genes 1, 2 and 3) with their directions of transcription (arrows) are also shown. The duplicate sequences may pair up, forming a stem and loop, and undergo recombination. The result is an inversion of the region between the duplicate sequences. This reverses the direction of transcription of the three enclosed genes with respect to the DNA molecule.
Oxidative damage to DNA is also significant. Hydroxyl and superoxide radicals derived from molecular oxygen will attack several bases. The most common target is guanine, which is oxidized to 8-hydroxy-guanine, which pairs preferentially with A. Hence a G • C base pair may be mutated into a T • A pair.
Non-enzymatic methylation of bases occurs at a low frequency. The methyl donor, S-adenosyl-methionine, is normally used by enzymes that attach methyl groups to their substrates. However, it is sufficiently reactive to attack several bases at a low rate spontaneously. The major problem is the formation of 3-methyl-adenine, which tends to block DNA elongation.
Occasionally, the bonds linking the bases of DNA to deoxyribose may spontaneously hydrolyze. This occurs more often with purines than with pyrimidines, generating empty, apurinic sites. Such missing bases tend to block DNA replication and are also an invitation to DNA polymerase to insert an incorrect base.
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