title: The spindle checkpoint of Saccharomyces cerevisiae responds to separable microtubule-dependent events.
abstract: The spindle checkpoint regulates microtubule-based chromosome segregation and helps to maintain genomic stability [1,2]. Mutational inactivation of spindle checkpoint genes has been implicated in the progression of several types of human cancer. Recent evidence from budding yeast suggests that the spindle checkpoint is complex. Order-of-function experiments have defined two separable pathways within the checkpoint. One pathway, defined by MAD2, controls the metaphase-to-anaphase transition and the other, defined by BUB2, controls the exit from mitosis [3-6]. The relationships between the separate branches of the checkpoint, and especially the events that trigger the pathways, have not been defined. We localized a Bub2p-GFP fusion protein to the cytoplasmic side of the spindle pole body and used a kar9 mutant to show that cells with misoriented spindles are arrested in anaphase of mitosis. We used a kar9 bub2 double mutant to show that the arrest is BUB2 dependent. We conclude that the separate pathways of the spindle checkpoint respond to different classes of microtubules. The MAD2 branch of the pathway responds to kinetochore microtubule interactions and the BUB2 branch of the pathway operates within the cytoplasm, responding to spindle misorientation.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia Medical Center, Charlottesville, Virginia 22908-0733, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Daum
authors.forename: N
authors.initials: N
authors.lastname: Gomez-Ospina
authors.forename: M
authors.initials: M
authors.lastname: Winey
authors.forename: D J
authors.initials: DJ
authors.lastname: Burke
mesh_terms: D002135:Calcium-Binding Proteins / Q000378:metabolism; D002352:Carrier Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017930:Genes, Reporter; D018816:Genes, cdc; D064246:Mad2 Proteins; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D008941:Spindle Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D014404:Tubulin / Q000276:immunology / Q000378:metabolism
chemical_list: C070351:BUB2 protein, S cerevisiae; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; C110443:KAR9 protein, S cerevisiae; C577695:MAD2 protein, S cerevisiae; D064246:Mad2 Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014404:Tubulin