Spontaneous Replication Errors

Replication is amazingly accurate: fewer than one in a billion errors are made in the course of DNA synthesis (Chapter 12). However, spontaneous replication errors do occasionally occur.

The primary cause of spontaneous replication errors was formerly thought to be tautomeric shifts, in which the positions of protons in the DNA bases change. Purine and pyrimidine bases exist in different chemical forms called tautomers (Figure 17.11a). The two tautomeric forms of each base are in dynamic equilibrium, although one form is more common than the other. The standard Watson and Crick base pairings—adenine with thymine, and cytosine with guanine—are between the common forms of the bases, but, if the bases are in their rare tautomeric forms, other base pairings are possible (< Figure 17.11b).

Watson and Crick proposed that tautomeric shifts might produce mutations, and for many years their proposal was the accepted model for spontaneous replication errors, but there has never been convincing evidence that the rare tautomers are the cause of spontaneous mutations. Furthermore, research now shows little evidence of these structures in DNA.

Mispairing can also occur through wobble, in which normal, protonated, and other forms of the bases are

17.11 Purine and pyrimidine bases exist in different forms called tautomers. (a) A tautomeric shift occurs when a proton changes its position, resulting in a rare tautomeric form. (b) Standard and anomalous base-pairing arrangements occur if bases are in the rare tautomeric forms. Base mispairings due to tautomeric shifts were originally thought to be a major source of errors in replication, but such structures have not been detected in DNA, and most evidence now suggests that other types of anomalous pairings (see Figure 17.14) are responsible for replication errors.

Common forms o^^roton shift

Rare forms

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