title: Transposon-mediated directed mutation in bacteria and eukaryotes.
abstract: Transposon-mediated "directed" mutations occur at higher frequencies when beneficial than when detrimental and relieve the stress that causes them. The first and best-studied example involves regulation of Insertion Sequence-5 (IS5) insertion into a specific activating site upstream of the glycerol utilization operon inEscherichia coli,glpFK. This event promotes high level expression of theglpFKoperon, allowing glycerol utilization in wild type cells under inhibitory conditions. The phosphoenolpyruvate-dependent, sugar transporting, phosphotransferase system (PTS) influences this process by regulating cytoplasmic glycerol-3-phosphate and cyclic AMP concentrations. Insertion frequencies are determined by IS5-specific tetranucleotide target sequences in stress-induced (DNA) duplex destabilization (SIDD) structures counteracted by two DNA binding proteins, GlpR and Crp which directly inhibit insertion, responding to cytoplasmic glycerol-3-phosphate and cyclic AMP, respectively. Expression of theE. colimaster regulator of flagellar gene control,flhDC, is subject to activation by IS elements by a directed mechanism, and zinc-induced transposon-mediated zinc resistance has been demonstrated inCupriavidus metallidurans. The use of DNA conformation and DNA binding proteins to control transposon hopping also occurs in eukaryotes.
authors.affiliation: Department of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093-0116, msaier@ucsd.edu.
authors.forename: Milton H
authors.initials: MH
authors.lastname: Saier
authors.affiliation: Department of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093-0116.
authors.forename: Chika
authors.initials: C
authors.lastname: Kukita
authors.affiliation: Department of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093-0116.
authors.forename: Zhongge
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D001419:Bacteria / Q000235:genetics*; D049921:Cupriavidus / Q000187:drug effects / Q000235:genetics; D004251:DNA Transposable Elements; D004926:Escherichia coli / Q000235:genetics; D056890:Eukaryota / Q000235:genetics*; D019143:Evolution, Molecular; D009154:Mutation; D009876:Operon; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System / Q000235:genetics; D015032:Zinc / Q000494:pharmacology
chemical_list: D004251:DNA Transposable Elements; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System; D015032:Zinc