title: Uncoupling the chemical steps of telomere resolution by ResT.
abstract: ResT is the telomere resolvase of the spirochete Borrelia burgdorferi, the causative agent of Lyme disease. ResT is an essential cellular function that processes replication intermediates to produce linear replicons terminated by covalently closed hairpin telomeres. ResT generates these hairpin telomeres in a reaction with mechanistic similarities to those catalyzed by type IB topoisomerases and tyrosine recombinases. We report here, that like most of the tyrosine recombinases, ResT requires interprotomer communication, likely in an in-line synapse, to activate reaction chemistry. Unlike the tyrosine recombinases, however, we infer that the cleavage and strand transfer reactions on the two sides of the replicated telomere occur nearly simultaneously. Nonetheless, the chemical steps of the forward and reverse reactions performed by ResT can occur in a non-concerted fashion (i.e. events on the two sides of the replicated telomere can occur independently). We propose that uncoupling of reaction completion on the two sides of the substrate is facilitated by an early commitment to hairpin formation that is imposed by the precleavage action of the hairpin binding module of the ResT active site.
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
authors.forename: Kerri
authors.initials: K
authors.lastname: Kobryn
authors.forename: Alex B
authors.initials: AB
authors.lastname: Burgin
authors.forename: George
authors.initials: G
authors.lastname: Chaconas
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics*; D001665:Binding Sites; D025065:Borrelia burgdorferi / Q000201:enzymology*; D004261:DNA Replication; D004706:Endodeoxyribonucleases / Q000235:genetics*; D009690:Nucleic Acid Conformation; D045522:Recombinases / Q000235:genetics; D012093:Replicon; D016615:Telomere / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D045522:Recombinases; D004706:Endodeoxyribonucleases; C446515:ResT protein, Borrelia