title: Protein motion from non-specific to specific DNA by three-dimensional routes aided by supercoiling.
abstract: DNA-binding proteins are generally thought to locate their target sites by first associating with the DNA at random and then translocating to the specific site by one-dimensional (1D) diffusion along the DNA. We report here that non-specific DNA conveys proteins to their target sites just as well when held near the target by catenation as when co-linear with the target. Hence, contrary to the prevalent view, proteins move from random to specific sites primarily by three-dimensional (3D) rather than 1D pathways, by multiple dissociation/re-association events within a single DNA molecule. We also uncover a role for DNA supercoiling in target-site location. Proteins find their sites more readily in supercoiled than in relaxed DNA, again indicating 3D rather than 1D routes.
authors.affiliation: Department of Biochemistry, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK.
authors.forename: Darren M
authors.initials: DM
authors.lastname: Gowers
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Halford
mesh_terms: D000873:Anthracenes / Q000737:chemistry; D001483:Base Sequence; D004262:DNA Restriction Enzymes / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D004269:DNA, Bacterial / Q000737:chemistry / Q000378:metabolism*; D004278:DNA, Superhelical / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004926:Escherichia coli / Q000737:chemistry; D007700:Kinetics; D009038:Motion; D009690:Nucleic Acid Conformation; D010957:Plasmids / Q000737:chemistry; D011083:Polycyclic Compounds / Q000737:chemistry; D021381:Protein Transport; D011994:Recombinant Proteins / Q000378:metabolism; D045522:Recombinases; D011995:Recombination, Genetic; D013379:Substrate Specificity; D019895:Transposases / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D000873:Anthracenes; D004269:DNA, Bacterial; D004278:DNA, Superhelical; D004268:DNA-Binding Proteins; D011083:Polycyclic Compounds; D011994:Recombinant Proteins; D045522:Recombinases; C467767:catenane; D019895:Transposases; D004262:DNA Restriction Enzymes