title: Hin-mediated DNA knotting and recombining promote replicon dysfunction and mutation.
abstract: BACKGROUND
  The genetic code imposes a dilemma for cells. The DNA must be long enough to encode for the complexity of an organism, yet thin and flexible enough to fit within the cell. The combination of these properties greatly favors DNA collisions, which can knot and drive recombination of the DNA. Despite the well-accepted propensity of cellular DNA to collide and react with itself, it has not been established what the physiological consequences are.
  
  
  RESULTS
  Here we analyze the effects of recombined and knotted plasmids in E. coli using the Hin site-specific recombination system. We show that Hin-mediated DNA knotting and recombination (i) promote replicon loss by blocking DNA replication; (ii) block gene transcription; and (iii) cause genetic rearrangements at a rate three to four orders of magnitude higher than the rate for an unknotted, unrecombined plasmid.
  
  
  CONCLUSIONS
  These results show that DNA reactivity leading to recombined and knotted DNA is potentially toxic and may help drive genetic evolution.
authors.affiliation: Interdepartmental Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030-3411, USA. richard_deibler@hms.harvard.edu <richard_deibler@hms.harvard.edu>
authors.forename: Richard W
authors.initials: RW
authors.lastname: Deibler
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Mann
authors.forename: De Witt L
authors.initials: de WL
authors.lastname: Sumners
authors.forename: Lynn
authors.initials: L
authors.lastname: Zechiedrich
mesh_terms: D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004254:DNA Nucleotidyltransferases / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D017930:Genes, Reporter; D009154:Mutation; D009690:Nucleic Acid Conformation; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D012093:Replicon / Q000235:genetics; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism
chemical_list: D004247:DNA; D004254:DNA Nucleotidyltransferases; C059997:Hin recombinase; D001618:beta-Lactamases