Transcriptional de-repression and Mfd are mutagenic in stressed Bacillus subtilis cells.

Abstract

In recent years, it has been proposed that conflicts between transcription and active chromosomal replication engender genome instability events. Furthermore, transcription elongation factors have been reported to prevent conflicts between transcription and replication and avoid genome instability. Here, we examined transcriptional de-repression as a genetic diversity-producing agent and showed, through the use of physiological and genetic means, that transcriptional de-represssion of a leuC defective allele leads to accumulation of Leu(+) mutations. We also showed, by using riboswitches that activate transcription in conditions of tyrosine or methionine starvation, that the effect of transcriptional de-repression of the leuC construct on the accumulation of Leu(+) mutations was independent of selection. We examined the role of Mfd, a transcription elongation factor involved in DNA repair, in this process and showed that proficiency of this factor promotes mutagenic events. These results are in stark contrast to previous reports in Escherichia coli, which showed that Mfd prevents replication fork collapses. Because our assays place cells under non-growing conditions, by starving them for two amino acids, we surmised that the Mfd mutagenic process associated with transcriptional de-repression does not result from conflicts with chromosomal replication. These results raise the interesting concept that transcription elongation factors may serve two functions in cells. In growing conditions, these factors prevent the generation of mutations, while in stress or non-growing conditions they mediate the production of genetic diversity.

• Authors: Holly Anne Martin, Mario Pedraza-Reyes, Ronald E Yasbin, Eduardo A Robleto
• Journal: Journal of molecular microbiology and biotechnology (J Mol Microbiol Biotechnol) Vol. 21 Issue 1-2 Pg. 45-58 ( 2011) ISSN: 1660-2412 [Electronic] Switzerland
• PMID: 22248542 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2012 S. Karger AG, Basel.

Chemical References

• Bacterial Proteins
• Transcription Factors
• transcription repair coupling factor protein, Bacteria
• Hydro-Lyases
• LeuC protein, bacteria

Topics

• Bacillus subtilis (genetics, physiology)
• Bacterial Proteins (genetics, metabolism)
• Escherichia coli (genetics, physiology)
• Genetic Variation
• Hydro-Lyases (deficiency, genetics)
• Mutation
• Stress, Physiological
• Transcription Factors (deficiency, genetics, metabolism)
• Transcription, Genetic
• Transcriptional Activation