title: Topo IV is the topoisomerase that knots and unknots sister duplexes during DNA replication.
abstract: DNA topology plays a crucial role in all living cells. In prokaryotes, negative supercoiling is required to initiate replication and either negative or positive supercoiling assists decatenation. The role of DNA knots, however, remains a mystery. Knots are very harmful for cells if not removed efficiently, but DNA molecules become knotted in vivo. If knots are deleterious, why then does DNA become knotted? Here, we used classical genetics, high-resolution 2D agarose gel electrophoresis and atomic force microscopy to show that topoisomerase IV (Topo IV), one of the two type-II DNA topoisomerases in bacteria, is responsible for the knotting and unknotting of sister duplexes during DNA replication. We propose that when progression of the replication forks is impaired, sister duplexes become loosely intertwined. Under these conditions, Topo IV inadvertently makes the strand passages that lead to the formation of knots and removes them later on to allow their correct segregation.
authors.affiliation: Departamento de Proliferación Celular y Desarrollo, Centro de Investigaciones Biológicas (CSIC), Ramiro de Maeztu 9, 28040 Madrid, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: López
authors.forename: María-Luisa
authors.initials: ML
authors.lastname: Martínez-Robles
authors.forename: Pablo
authors.initials: P
authors.lastname: Hernández
authors.forename: Dora B
authors.initials: DB
authors.lastname: Krimer
authors.forename: Jorge B
authors.initials: JB
authors.lastname: Schvartzman
mesh_terms: D004261:DNA Replication; D027101:DNA Topoisomerase IV / Q000378:metabolism*; D004269:DNA, Bacterial / Q000737:chemistry / Q000648:ultrastructure*; D043864:DNA, Catenated / Q000737:chemistry; D018625:Microscopy, Atomic Force; D009690:Nucleic Acid Conformation
chemical_list: D004269:DNA, Bacterial; D043864:DNA, Catenated; D027101:DNA Topoisomerase IV