title: Reverse gyrase--recent advances and current mechanistic understanding of positive DNA supercoiling.
abstract: Reverse gyrases are topoisomerases that introduce positive supercoils into DNA in an ATP-dependent reaction. They consist of a helicase domain and a topoisomerase domain that closely cooperate in catalysis. The mechanism of the functional cooperation of these domains has remained elusive. Recent studies have shown that the helicase domain is a nucleotide-regulated conformational switch that alternates between an open conformation with a low affinity for double-stranded DNA, and a closed state with a high double-stranded DNA affinity. The conformational cycle leads to transient separation of DNA duplexes by the helicase domain. Reverse gyrase-specific insertions in the helicase module are involved in binding to single-stranded DNA regions, DNA unwinding and supercoiling. Biochemical and structural data suggest that DNA processing by reverse gyrase is not based on sequential action of the helicase and topoisomerase domains, but rather the result of an intricate cooperation of both domains at all stages of the reaction. This review summarizes the recent advances of our understanding of the reverse gyrase mechanism. We put forward and discuss a refined, yet simple model in which reverse gyrase directs strand passage toward increasing linking numbers and positive supercoiling by controlling the conformation of a bound DNA bubble.
authors.affiliation: University of Muenster, Institute for Physical Chemistry, Corrensstrasse 30, D-48149 Muenster, Germany.
authors.forename: Pavel
authors.initials: P
authors.lastname: Lulchev
authors.affiliation: University of Muenster, Institute for Physical Chemistry, Corrensstrasse 30, D-48149 Muenster, Germany dagmar.klostermeier@uni-muenster.de.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Klostermeier
mesh_terms: D004264:DNA Topoisomerases, Type I / Q000737:chemistry* / Q000378:metabolism; D004278:DNA, Superhelical / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004278:DNA, Superhelical; C041813:DNA reverse gyrase; D004264:DNA Topoisomerases, Type I