title: A cell cycle-controlled redox switch regulates the topoisomerase IV activity.
abstract: Topoisomerase IV (topo IV), an essential factor during chromosome segregation, resolves the catenated chromosomes at the end of each replication cycle. How the decatenating activity of the topo IV is regulated during the early stages of the chromosome cycle despite being in continuous association with the chromosome remains poorly understood. Here we report a novel cell cycle-regulated protein in Caulobacter crescentus, NstA (negative switch for topo IV decatenation activity), that inhibits the decatenation activity of the topo IV during early stages of the cell cycle. We demonstrate that in C. crescentus, NstA acts by binding to the ParC DNA-binding subunit of topo IV. Most importantly, we uncover a dynamic oscillation of the intracellular redox state during the cell cycle, which correlates with and controls NstA activity. Thus, we propose that predetermined dynamic intracellular redox fluctuations may act as a global regulatory switch to control cellular development and cell cycle progression and may help retain pathogens in a suitable cell cycle state when encountering redox stress from the host immune response.
authors.affiliation: School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram 695016, Kerala, India.
authors.forename: Sharath
authors.initials: S
authors.lastname: Narayanan
authors.affiliation: School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram 695016, Kerala, India.
authors.forename: Balaganesh
authors.initials: B
authors.lastname: Janakiraman
authors.affiliation: School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram 695016, Kerala, India.
authors.forename: Lokesh
authors.initials: L
authors.lastname: Kumar
authors.affiliation: School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram 695016, Kerala, India sunish@iisertvm.ac.in.
authors.forename: Sunish Kumar
authors.initials: SK
authors.lastname: Radhakrishnan
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D016935:Caulobacter crescentus / Q000201:enzymology* / Q000254:growth & development; D002453:Cell Cycle / Q000502:physiology*; D027101:DNA Topoisomerase IV / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D005812:Genes, Switch / Q000502:physiology*; D010084:Oxidation-Reduction; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D021122:Protein Subunits; D027101:DNA Topoisomerase IV
keywords: Caulobacter crescentus; ClpXP proteolysis; DNA decatenation; cell cycle; chromosome segregation; intracellular redox; topoisomerase IV