PMID:16430690

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Citation

Pham, PT, Zhao, W and Schaaper, RM (2006) Mutator mutants of Escherichia coli carrying a defect in the DNA polymerase III tau subunit. Mol. Microbiol. 59:1149-61

Abstract

To investigate the possible role of accessory subunits of Escherichia coli DNA polymerase III holoenzyme (HE) in determining chromosomal replication fidelity, we have investigated the role of the dnaX gene. This gene encodes both the tau and gamma subunits of HE, which play a central role in the organization and functioning of HE at the replication fork. We find that a classical, temperature-sensitive dnaX allele, dnaX36, displays a pronounced mutator effect, characterized by an unusual specificity: preferential enhancement of transversions and -1 frameshifts. The latter occur predominantly at non-run sequences. The dnaX36 defect does not affect the gamma subunit, but produces a tau subunit carrying a missense substitution (E601K) in its C-terminal domain (domain V) that is involved in interaction with the Pol III alpha subunit. A search for new mutators in the dnaX region of the chromosome yielded six additional dnaX mutators, all carrying a specific tau subunit defect. The new mutators displayed phenotypes similar to dnaX36: strong enhancement of transversions and frameshifts and only weak enhancement for transitions. The combined findings suggest that the tau subunit of HE plays an important role in determining the fidelity of the chromosomal replication, specifically in the avoidance of transversions and frameshift mutations.

Links

PubMed Online version:10.1111/j.1365-2958.2005.05011.x

Keywords

Alleles; Amino Acid Substitution; Bacterial Proteins/genetics; Bacterial Proteins/physiology; Base Sequence; DNA Polymerase III/genetics; DNA Polymerase III/physiology; DNA Replication/genetics; Escherichia coli/enzymology; Escherichia coli/genetics; Escherichia coli Proteins/genetics; Escherichia coli Proteins/physiology; Frameshift Mutation; Holoenzymes/genetics; Holoenzymes/physiology; Molecular Sequence Data; Mutagenesis/genetics; Mutation, Missense; Transcription Factors/genetics; Transcription Factors/physiology

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