title: The RSC chromatin-remodeling complex influences mitotic exit and adaptation to the spindle assembly checkpoint by controlling the Cdc14 phosphatase.
abstract: Upon prolonged activation of the spindle assembly checkpoint, cells escape from mitosis through a mechanism called adaptation or mitotic slippage, which is thought to underlie the resistance of cancer cells to antimitotic drugs. We show that, in budding yeast, this mechanism depends on known essential and nonessential regulators of mitotic exit, such as the Cdc14 early anaphase release (FEAR) pathway for the release of the Cdc14 phosphatase from the nucleolus in early anaphase. Moreover, the RSC (remodel the structure of chromatin) chromatin-remodeling complex bound to its accessory subunit Rsc2 is involved in this process as a novel component of the FEAR pathway. We show that Rsc2 interacts physically with the polo kinase Cdc5 and is required for timely phosphorylation of the Cdc14 inhibitor Net1, which is important to free Cdc14 in the active form. Our data suggest that fine-tuning regulators of mitotic exit have important functions during mitotic progression in cells treated with microtubule poisons and might be promising targets for cancer treatment.
authors.affiliation: Dipartimento di Biotecnologie e Bioscienze, Università degli Studi di Milano-Bicocca, 20126 Milano, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Rossio
authors.forename: Elena
authors.initials: E
authors.lastname: Galati
authors.forename: Matteo
authors.initials: M
authors.lastname: Ferrari
authors.forename: Achille
authors.initials: A
authors.lastname: Pellicioli
authors.forename: Takashi
authors.initials: T
authors.lastname: Sutani
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Shirahige
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lucchini
authors.forename: Simonetta
authors.initials: S
authors.lastname: Piatti
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D018816:Genes, cdc; D008938:Mitosis / Q000502:physiology*; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000502:physiology*
chemical_list: C074860:CDC14 protein, S cerevisiae; D018797:Cell Cycle Proteins; D029701:Saccharomyces cerevisiae Proteins; D010749:Phosphoprotein Phosphatases; D017027:Protein Tyrosine Phosphatases