Hypermutation in Derepressed Operons of Escherichia coli K12

This article presents evidence that starvation for leucine in an Escherichia coli auxotroph triggers metabolic activities that specifically target the leu operon for derepression, increased rates of transcription, and mutation. Derepression of the leu operon was a prerequisite for its activation by...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1999-04, Vol.96 (9), p.5089-5094
Main Authors: Wright, Barbara E., Longacre, Angelika, Reimers, Jacqueline M.
Format: Article
Language:English
Subjects:
Amino acids
Bacteria
Biological Sciences
DNA
Escherichia coli
Escherichia coli - genetics
Evolution
Gene Expression Regulation, Bacterial
Genes
Genetic mutation
Leucine - genetics
Messenger RNA
Mutation
Operon - genetics
Operons
Plasmids
RNA
RNA, Bacterial - genetics
RNA, Messenger - genetics
Starvation
Transcription, Genetic
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Summary:This article presents evidence that starvation for leucine in an Escherichia coli auxotroph triggers metabolic activities that specifically target the leu operon for derepression, increased rates of transcription, and mutation. Derepression of the leu operon was a prerequisite for its activation by the signal nucleotide, guanosine tetraphosphate, which accumulates in response to nutritional stress (the stringent response). A quantitative correlation was established between leuB mRNA abundance and leuB-reversion rates. To further demonstrate that derepression increased mutation rates, the chromosomal leu operon was placed under the control of the inducible tac promoter. When the leu operon was induced by isopropyl-D-thiogalactoside, both leuB mRNA abundance and leuB-reversion rates increased. These investigations suggest that guanosine tetraphosphate may contribute as much as attenuation in regulating leu operon expression and that higher rates of mutation are specifically associated with the derepressed leu operon.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.96.9.5089