{"doi":"10.1073/pnas.96.9.5089","title":"Hypermutation in derepressed operons of<i>Escherichia coli</i>K12","abstract":"<jats:p>This article presents evidence that starvation for leucine in an<jats:italic>Escherichia coli</jats:italic>auxotroph triggers metabolic activities that specifically target the<jats:italic>leu</jats:italic>operon for derepression, increased rates of transcription, and mutation. Derepression of the<jats:italic>leu</jats:italic>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<jats:italic>leuB</jats:italic>mRNA abundance and<jats:italic>leuB</jats:italic><jats:sup>−</jats:sup>reversion rates. To further demonstrate that derepression increased mutation rates, the chromosomal<jats:italic>leu</jats:italic>operon was placed under the control of the inducible<jats:italic>tac</jats:italic>promoter. When the<jats:italic>leu</jats:italic>operon was induced by isopropyl-<jats:sc>d</jats:sc>-thiogalactoside, both<jats:italic>leuB</jats:italic>mRNA abundance and<jats:italic>leuB</jats:italic><jats:sup>−</jats:sup>reversion rates increased. These investigations suggest that guanosine tetraphosphate may contribute as much as attenuation in regulating<jats:italic>leu</jats:italic>operon expression and that higher rates of mutation are specifically associated with the derepressed<jats:italic>leu</jats:italic>operon.</jats:p>","journal":"Proceedings of the National Academy of Sciences","year":1999,"id":16629,"datarank":4.514728335496189,"base_score":4.304065093204169,"endowment":4.304065093204169,"self_citation_contribution":0.6456097639806255,"citation_network_contribution":3.869118571515563,"self_endowment_contribution":0.6456097639806255,"citer_contribution":3.869118571515563,"corpus_percentile":null,"corpus_rank":null,"citation_count":73,"citer_count":63,"citers_with_citation_signal":60,"citers_with_endowment":60,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":122014,"name":"Angelika Longacre","orcid":null,"position":1,"is_corresponding":false},{"id":122015,"name":"Jacqueline M. 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