Introduction: Avoidance of Spontaneously Occurring Errors in DNA
In order to perpetuate species homogeneity, DNA replication must be an exceptionally accurate process. Yet, a small number of mistakes in DNA replication must also be permitted to promote species evolution. The mechanism for achieving high fidelity with bacterial systems has been investigated extensively. The major contributors to accuracy are the DNA polymerases themselves. Alterations in DNA polymerases and associated proteins can modulate fidelity and effect mutagenesis. In animal cells, the accuracy of DNA replication is likely to be even higher than in bacteria. Measurements of spontaneous mutation frequencies in animal cells suggest that the average frequency of errors in DNA replication is in the range of 10−9 to 10−11 errors per base pair replicated. This value is the net result of errors made during DNA replication and repair minus the correction of these mistakes by processes such as mismatch correction.