title: Gross chromosomal rearrangement mediated by DNA replication in stressed cells: evidence from Escherichia coli.
abstract: Gross chromosomal rearrangements (GCRs), or changes in chromosome structure, play central roles in evolution and are central to cancer formation and progression. GCRs underlie copy number variation (CNV), and therefore genomic disorders that stem from CNV. We study amplification in Escherichia coli as a model system to understand mechanisms and circumstances of GCR formation. Here, we summarize observations that led us to postulate that GCR occurs by a replicative mechanism as part of activated stress responses. We report that we do not find RecA to be downregulated by stress on a population basis and that constitutive expression of RecA does not inhibit amplification, as would be expected if downregulation of RecA made cells permissive for nonhomologous recombination. Strains deleted for the genes for three proteins that inhibit RecA activity, psiB, dinI, and recX, all show unaltered amplification, suggesting that if they do downregulate RecA indirectly, this activity does not promote amplification.
authors.affiliation: Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Moore
authors.forename: Hallie
authors.initials: H
authors.lastname: Wimberly
authors.forename: P C
authors.initials: PC
authors.lastname: Thornton
authors.forename: Susan M
authors.initials: SM
authors.lastname: Rosenberg
authors.forename: P J
authors.initials: PJ
authors.lastname: Hastings
mesh_terms: D002876:Chromosomes, Bacterial / Q000235:genetics*; D056915:DNA Copy Number Variations; D059766:DNA End-Joining Repair; D004261:DNA Replication; D004269:DNA, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics* / Q000502:physiology; D005784:Gene Amplification; D015321:Gene Rearrangement; D017354:Point Mutation; D013312:Stress, Physiological / Q000235:genetics*
chemical_list: D004269:DNA, Bacterial