Error-Prone Polymerase, DNA Polymerase IV, Is Responsible for Transient Hypermutation during Adaptive Mutation in Escherichia coli

Abstract

The frequencies of nonselected mutations among adaptive Lac؉ revertants of Escherichia coli strains with and without the error-prone DNA polymerase IV (Pol IV) were compared. This frequency was more than sevenfold lower in the Pol IV-defective strain than in the wild-type strain. Thus, the mutations that occur during hypermutation are due to Pol IV.

Stress responses and genetic variation in bacteria

“…In E. coli strain FC40 hypermutation requires Pol IV [69]; in addition, mismatch repair is not active among hypermutators [63]. Thus, the hypermutator state appears to be due to the combination of induced expression of Pol IV plus decreased activity of mismatch repair in a small subpopulation of cells [69,63].…”

“…Thus, the hypermutator state appears to be due to the combination of induced expression of Pol IV plus decreased activity of mismatch repair in a small subpopulation of cells [69,63]. About 0.1% of the population are hypermutators and their mutation rate is elevated about 200-fold.…”

The optimal burst of mutation to create a phenotype

“…If the lethal fraction was relatively invariant across environments, then a strategy matching U ̅ L = D could be achieved merely as a fixed number of new mutations in the genome (or any portion of a genome) after a single episode of error prone replication. Furthermore, some infrequently used polymerases that are error prone could provide a mechanism to do so (Bull et al, 2001;Tompkins et al, 2003). While such a mechanism seems unprecedented, it should be possible to test whether bacteria behave in the appropriate fashion when challenged with harsh environments.…”

“…There has been far less attention to the evolutionary consequences of mutation pulses, perhaps because they seem unnatural. Nonetheless, mutation pulses are used in industrial attempts to create novel molecules (Shafikhani et al, 1997;Drummond et al, 2005;Rowe et al, 2003), and they may also operate in nature, as when a cell induces an error prone DNA polymerase for repair (Tompkins et al, 2003) or during biofilm progression (Boles et al, 2004).…”

Proficient and Accurate Bypass of Persistent DNA Lesions by DinB DNA Polymerases

“…2), has recently been elucidated. [8][9][10][11][12] Although identified in the first functional screen for transcripts upregulated upon DNA damage in Escherichia coli, 13 an absence of striking and genetically tractable phenotypes, particularly relative to its homologs, resulted in comparatively few insights into DinB function. Here we will summarize the data regarding DinB/pol k dependent mutagenesis and propose a revised view of its function as a specialized DNA polymerase with mutagenic potential that arises along with its unique substrate specificity.…”