The spindle checkpoint: structural insights into dynamic signalling View Full Text


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Article Info

DATE

2002-10

AUTHORS

Andrea Musacchio, Kevin G. Hardwick

ABSTRACT

Key Points The spindle checkpoint monitors the interactions between chromosomes and microtubules. The Mad and Bub proteins are core components of this cell-cycle control. The checkpoint can monitor kinetochore–microtubule attachment and/or the tension exerted at kinetochores upon bipolar attachment. Kinetochores are a key site for monitoring defects and signalling, and for effecting the cell-cycle delay. They can act as the catalytic site for the production of the checkpoint signal ('wait anaphase'), which must then be transmitted globally. Microtubule motors (CENP-E and dynein) and protein kinases (Aurora B) have roles in kinetochore binding and bipolar attachment, and could be involved in sensing tension. Mad2 and other checkpoint proteins have a very dynamic association with kinetochores (half-life of ∼20 s). These dynamics might also be involved in checkpoint silencing. Several checkpoint components (Mad2, BubR1, CENP-E and Rod) are continuously removed from kinetochores by a dynein-dependent mechanism. Two related interactions of Mad2 (with Mad1 and Cdc20) are central to the checkpoint, and crystal structures of a Mad1–Mad2 complex have revealed a 'safety-belt' bind-and-release mechanism. Mad2 and/or BubR1 complexes might stoichiometrically inhibit Cdc20 and thereby the activity of the anaphase-promoting complex. More... »

PAGES

731-741

References to SciGraph publications

  • 1998-03. Mutations of mitotic checkpoint genes in human cancers in NATURE
  • 2001-07. A MAP kinase-dependent actin checkpoint ensures proper spindle orientation in fission yeast in NATURE
  • 2001-01. MAD2 haplo-insufficiency causes premature anaphase and chromosome instability in mammalian cells in NATURE
  • 2000-03. Structure of the Mad2 spindle assembly checkpoint protein and its interaction with Cdc20 in NATURE STRUCTURAL & MOLECULAR BIOLOGY
  • 2000-11-14. Human Zw10 and ROD are mitotic checkpoint proteins that bind to kinetochores in NATURE CELL BIOLOGY
  • 2000-11-14. Cytoplasmic dynein is required for poleward chromosome movement during mitosis in Drosophila embryos in NATURE CELL BIOLOGY
  • 2000-11-14. Rough Deal and Zw10 are required for the metaphase checkpoint in Drosophila in NATURE CELL BIOLOGY
  • 2000-07-19. Anaphase spindle position is monitored by the BUB2 checkpoint in NATURE CELL BIOLOGY
  • 2000-09-21. p55CDC/hCDC20 is associated with BUBR1 and may be a downstream target of the spindle checkpoint kinase in ONCOGENE
  • 2001-10-11. Kinetochore dynein: its dynamics and role in the transport of the Rough deal checkpoint protein in NATURE CELL BIOLOGY
  • 1999-07. Sister-chromatid separation at anaphase onset is promoted by cleavage of the cohesin subunit Scc1 in NATURE
  • 2001-09. Evolutionary conservation between budding yeast and human kinetochores in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 1998-12. The hBUB1 and hBUBR1 kinases sequentially assemble onto kinetochores during prophase with hBUBR1 concentrating at the kinetochore plates in mitosis in CHROMOSOMA
  • 1998-12. Localization of the Drosophila checkpoint control protein Bub3 to the kinetochore requires Bub1 but not Zw10 or Rod in CHROMOSOMA
  • 2001-11. MEN and SIN: what's the difference? in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2000-07-10. CENP-E forms a link between attachment of spindle microtubules to kinetochores and the mitotic checkpoint in NATURE CELL BIOLOGY
  • 2001-04-11. Fission yeast Bub1 is essential in setting up the meiotic pattern of chromosome segregation in NATURE CELL BIOLOGY
  • 1995-02. Mitotic forces control a cell-cycle checkpoint in NATURE
  • 1999-11-11. Components of the spindle-assembly checkpoint are essential in Caenorhabditis elegans in NATURE CELL BIOLOGY
  • 2001-03-22. Mutations in the APC tumour suppressor gene cause chromosomal instability in NATURE CELL BIOLOGY
  • 2000-11-14. The rate of poleward chromosome motion is attenuated in Drosophila zw10 and rod mutants in NATURE CELL BIOLOGY
  • 2001-03-22. A role for the Adenomatous Polyposis Coli protein in chromosome segregation in NATURE CELL BIOLOGY
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    http://scigraph.springernature.com/pub.10.1038/nrm929

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    https://www.ncbi.nlm.nih.gov/pubmed/12360190


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