title: A mitotic topoisomerase II checkpoint in budding yeast is required for genome stability but acts independently of Pds1/securin.
abstract: Topoisomerase II (Topo II) performs topological modifications on double-stranded DNA molecules that are essential for chromosome condensation, resolution, and segregation. In mammals, G2 and metaphase cell cycle delays induced by Topo II poisons have been proposed to be the result of checkpoint activation in response to the catenation state of DNA. However, the apparent lack of such controls in model organisms has excluded genetic proof that Topo II checkpoints exist and are separable from the conventional DNA damage checkpoint controls. But here, we define a Topo II-dependent G2/M checkpoint in a genetically amenable eukaryote, budding yeast, and demonstrate that this checkpoint enhances cell survival. Conversely, a lack of the checkpoint results in aneuploidy. Neither DNA damage-responsive pathways nor Pds1/securin are needed for this checkpoint. Unusually, spindle assembly checkpoint components are required for the Topo II checkpoint, but checkpoint activation is not the result of failed chromosome biorientation or a lack of spindle tension. Thus, compromised Topo II function activates a yeast checkpoint system that operates by a novel mechanism.
authors.affiliation: Department of Genetics, Cell Biology and Development, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Andrews
authors.forename: Amit C
authors.initials: AC
authors.lastname: Vas
authors.forename: Brian
authors.initials: B
authors.lastname: Meier
authors.forename: Juan F
authors.initials: JF
authors.lastname: Giménez-Abián
authors.forename: Laura A
authors.initials: LA
authors.lastname: Díaz-Martínez
authors.forename: Julie
authors.initials: J
authors.lastname: Green
authors.forename: Stacy L
authors.initials: SL
authors.lastname: Erickson
authors.forename: Kristyn E
authors.initials: KE
authors.lastname: Vanderwaal
authors.forename: Wei-Shan
authors.initials: WS
authors.lastname: Hsu
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Clarke
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015825:Chromosomes, Fungal; D004249:DNA Damage; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000502:physiology*; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism; D016195:G2 Phase; D042822:Genomic Instability; D008938:Mitosis; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D064249:Securin; D064247:Separase; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C578004:PDS1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D064249:Securin; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; C099685:SWE1 protein, S cerevisiae; D011505:Protein-Tyrosine Kinases; D010450:Endopeptidases; D064247:Separase; D004250:DNA Topoisomerases, Type II