Replicational Fidelity: Mechanisms of Mutation Avoidance and Mutation Fixation

Abstract

Most spontaneous and induced mutations occur as mistakes during DNA synthesis. The low error rate (roughly 10−9/nucleotide replication in Escherichia coli: for review, see Cox [1976]) is achieved by the cellular enzymatic machinery. For example, prokaryotic DNA polymerases contribute to the fidelity of DNA synthesis through an active base selection and an associated 3′→5′ exonuclease, called proofreading or editing activity, as demonstrated by genetical and biochemical studies of mutator and antimutator mutants affecting DNA polymerase of bacteriophage T4 (Gillin and Nossal 1976; Ko-Yu and Bessman 1976). Mutations in T4 gene 32, coding for a DNA-binding protein, can also affect spontaneous mutation rates by an unknown mechanism (Drake 1973). Of the ten loci which are known mutators in E. coli, two of them (weak) have been shown to code for DNA polymerases I and III; for the other eight loci, which include powerful mutators, neither the gene product nor the mechanism...