title: p31(comet) acts to ensure timely spindle checkpoint silencing subsequent to kinetochore attachment.
abstract: The spindle assembly checkpoint links the onset of anaphase to completion of chromosome-microtubule attachment and is mediated by the binding of Mad and Bub proteins to kinetochores of unattached or maloriented chromosomes. Mad2 and BubR1 traffic between kinetochores and the cytosol, thereby transmitting a "wait anaphase" signal to the anaphase-promoting complex. It is generally assumed that this signal dissipates automatically upon kinetochore-microtubule binding, but it has been shown that under conditions of nocodazole-induced arrest p31(comet), a Mad2-binding protein, is required for mitotic progression. In this article we investigate the localization and function of p31(comet) during normal, unperturbed mitosis in human and marsupial cells. We find that, like Mad2, p31(comet) traffics on and off kinetochores and is also present in the cytosol. Cells depleted of p31(comet) arrest in metaphase with mature bipolar kinetochore-microtubule attachments, a satisfied checkpoint, and high cyclin B levels. Thus p31(comet) is required for timely mitotic exit. We propose that p31(comet) is an essential component of the machinery that silences the checkpoint during each cell cycle.
authors.affiliation: Center for Cell Decision Processes, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Hagan
authors.forename: Michael S
authors.initials: MS
authors.lastname: Manak
authors.forename: Håkon Kirkeby
authors.initials: HK
authors.lastname: Buch
authors.forename: Michelle G
authors.initials: MG
authors.lastname: Meier
authors.forename: Patrick
authors.initials: P
authors.lastname: Meraldi
authors.forename: Jagesh V
authors.initials: JV
authors.lastname: Shah
authors.forename: Peter K
authors.initials: PK
authors.lastname: Sorger
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D002877:Chromosomes, Human / Q000378:metabolism; D033481:Chromosomes, Mammalian / Q000378:metabolism; D019926:Cyclin B / Q000032:analysis; D003600:Cytosol; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D059566:M Phase Cell Cycle Checkpoints; D064246:Mad2 Proteins; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D015739:Nocodazole / Q000494:pharmacology; D009687:Nuclear Proteins / Q000378:metabolism*; D048328:Potoroidae; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport; D034622:RNA Interference; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D019926:Cyclin B; C577697:MAD2L1 protein, human; C470309:MAD2L1BP protein, human; D064246:Mad2 Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D050257:Tubulin Modulators; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases; D015739:Nocodazole