DNA replication fidelity in Escherichia coli: a multi-DNA polymerase affair

• Published in: FEMS microbiology reviews 2012-11, Vol.36 (6), p.1105-1121
• Main Authors: Fijalkowska, Iwona J., Schaaper, Roel M., Jonczyk, Piotr
• Format: Article
• Language: English
• Subjects: accessory DNA polymerases; Accuracy; Bacteriology; Base pairs; Biological and medical sciences; Deoxyribonucleic acid; DNA; DNA biosynthesis; DNA polymerase; DNA Replication; DNA replication fidelity; DNA, Bacterial - biosynthesis; DNA, Bacterial - genetics; DNA-directed DNA polymerase; DNA-Directed DNA Polymerase - metabolism; E coli; Escherichia coli; Escherichia coli - genetics; Escherichia coli - metabolism; Escherichia coli Proteins - metabolism; exonucleolytic proofreading; Fidelity; Fundamental and applied biological sciences. Psychology; Genetic analysis; Genetics; leading and lagging DNA replication; Low level; Microbiology; Mutation; Mutation rates; Okazaki fragments; polymerase switching; Replication; Reviews; untargeted mutagenesis
• ISSN: 0168-6445; 1574-6976; 1574-6976
• DOI: 10.1111/j.1574-6976.2012.00338.x

Abstract High accuracy (fidelity) of DNA replication is important for cells to preserve the genetic identity and to prevent the accumulation of deleterious mutations. The error rate during DNA replication is as low as 10−9 to 10−11 errors per base pair. How this low level is achieved is an issue of major interest. This review is concerned with the mechanisms underlying the fidelity of the chromosomal replication in the model system Escherichia coli by DNA polymerase III holoenzyme, with further emphasis on participation of the other, accessory DNA polymerases, of which E. coli contains four (Pols I, II, IV, and V). Detailed genetic analysis of mutation rates revealed that (1) Pol II has an important role as a back-up proofreader for Pol III, (2) Pols IV and V do not normally contribute significantly to replication fidelity, but can readily do so under conditions of elevated expression, (3) participation of Pols IV and V, in contrast to that of Pol II, is specific to the lagging strand, and (4) Pol I also makes a lagging-strand-specific fidelity contribution, limited, however, to the faithful filling of the Okazaki fragment gaps. The fidelity role of the Pol III τ subunit is also reviewed. This review is concerned with the mechanisms underlying the fidelity of the chromosomal replication in the model system Escherichia coli by DNA polymerase III holoenzyme (HE), with further emphasis on participation of the other, accessory DNA polymerases, of which E. coli contains four (Pols I, II, IV, and V).