title: Regulated inactivation of the spindle assembly checkpoint without functional mitotic spindles.
abstract: The spindle assembly checkpoint (SAC) arrests mitosis until bipolar attachment of spindle microtubules to all chromosomes is accomplished. However, when spindle formation is prevented and the SAC cannot be satisfied, mammalian cells can eventually overcome the mitotic arrest while the checkpoint is still activated. We find that Aspergillus nidulans cells, which are unable to satisfy the SAC, inactivate the checkpoint after a defined period of mitotic arrest. Such SAC inactivation allows normal nuclear reassembly and mitotic exit without DNA segregation. We demonstrate that the mechanisms, which govern such SAC inactivation, require protein synthesis and can occur independently of inactivation of the major mitotic regulator Cdk1/Cyclin B or mitotic exit. Moreover, in the continued absence of spindle function cells transit multiple cell cycles in which the SAC is reactivated each mitosis before again being inactivated. Such cyclic activation and inactivation of the SAC suggests that it is subject to cell-cycle regulation that is independent of bipolar spindle function.
authors.affiliation: Department of Molecular Genetics, Ohio State University, Columbus, OH, USA. de-souza.1@osu.edu
authors.forename: Colin P
authors.initials: CP
authors.lastname: De Souza
authors.forename: Shahr B
authors.initials: SB
authors.lastname: Hashmi
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Yang
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Osmani
mesh_terms: D001233:Aspergillus nidulans / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology; D048750:Cell Nucleus Division / Q000502:physiology; D049109:Cell Proliferation; D019926:Cyclin B / Q000378:metabolism; D015536:Down-Regulation; D018816:Genes, cdc / Q000502:physiology*; D008870:Microtubules / Q000378:metabolism / Q000502:physiology; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D030781:Organisms, Genetically Modified; D014176:Protein Biosynthesis / Q000502:physiology; D011499:Protein Processing, Post-Translational; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; D019926:Cyclin B