en
Scientific article
Open access
English

p31(comet) acts to ensure timely spindle checkpoint silencing subsequent to kinetochore attachment

Published inMolecular biology of the cell, vol. 22, no. 22, p. 4236-4246
Publication date2011
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.

Keywords
  • Adaptor Proteins, Signal Transducing/metabolism
  • Animals
  • Calcium-Binding Proteins/metabolism
  • Cell Cycle/drug effects
  • Cell Cycle Proteins/metabolism
  • Cell Line
  • Chromosomes, Human/metabolism
  • Chromosomes, Mammalian/metabolism
  • Cyclin B/analysis
  • Cytosol
  • Humans
  • Kinetochores/metabolism
  • M Phase Cell Cycle Checkpoints
  • Microtubules/metabolism
  • Mitosis/drug effects
  • Mitotic Spindle Apparatus/metabolism
  • Nocodazole/pharmacology
  • Nuclear Proteins/metabolism
  • Potoroidae
  • Protein Transport
  • Protein-Serine-Threonine Kinases/metabolism
  • RNA Interference
  • Repressor Proteins/metabolism
  • Signal Transduction
  • Tubulin Modulators/pharmacology
Affiliation Not a UNIGE publication
Citation (ISO format)
HAGAN, Robert S et al. p31(comet) acts to ensure timely spindle checkpoint silencing subsequent to kinetochore attachment. In: Molecular biology of the cell, 2011, vol. 22, n° 22, p. 4236–4246. doi: 10.1091/mbc.E11-03-0216
Main files (1)
Article (Published version)
accessLevelPublic
Identifiers
ISSN of the journal1059-1524
518views
290downloads

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