title: Studies on a "jumping gene machine": higher-order nucleoprotein complexes in Mu DNA transposition.
abstract: Studies in my lab have focused on DNA transposition in the bacterial virus, Mu. In vitro studies have shown that Mu DNA transposition is a three-step process involving DNA breakage, strand transfer and DNA replication. In the first step, a nick is introduced at each end of the transposon. The liberated 3'-OH groups subsequently attack a target DNA molecule resulting in strand transfer. The transposon DNA, now covalently linked to the target, is finally replicated to generate the transposition end-product, referred to as a cointegrate. The DNA cleavage and strand transfer reactions are mediated by a "jumping gene machine" or transpososomes, which we discovered in 1987. They are assembled by bringing together three different DNA regions via a process involving multiple protein-DNA and protein-protein interactions. The action of four different proteins is required in addition to protein-induced DNA bending or wrapping to overcome the intrinsic stiffness of DNA, which would ordinarily prohibit the assembly of such a structure. Transpososome assembly is a gradual process involving multiple steps with an inherent flexibility whereby alternate pathways can be used in the assembly process, biasing the reaction towards completion under different conditions.
authors.affiliation: Department of Biochemistry, University of Western Ontario, London, Canada. chaconas@julian.uwo.ca
authors.forename: G
authors.initials: G
authors.lastname: Chaconas
mesh_terms: D010583:Bacteriophage mu / Q000235:genetics* / Q000378:metabolism; D004261:DNA Replication; D004251:DNA Transposable Elements; D004742:Enhancer Elements, Genetic; D009698:Nucleoproteins / Q000378:metabolism*
chemical_list: D004251:DNA Transposable Elements; D009698:Nucleoproteins