Structure of the mitotic checkpoint complex
In mitosis, the spindle assembly checkpoint (SAC) ensures genome stability by delaying chromosome segregation until all sister chromatids have achieved bipolar attachment to the mitotic spindle. The SAC is imposed by the mitotic checkpoint complex (MCC), whose assembly is catalysed by unattached chr...
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Published in | Nature (London) Vol. 484; no. 7393; pp. 208 - 213 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
12.04.2012
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | In mitosis, the spindle assembly checkpoint (SAC) ensures genome stability by delaying chromosome segregation until all sister chromatids have achieved bipolar attachment to the mitotic spindle. The SAC is imposed by the mitotic checkpoint complex (MCC), whose assembly is catalysed by unattached chromosomes and which binds and inhibits the anaphase-promoting complex/cyclosome (APC/C), the E3 ubiquitin ligase that initiates chromosome segregation. Here, using the crystal structure of
Schizosaccharomyces pombe
MCC (a complex of mitotic spindle assembly checkpoint proteins Mad2, Mad3 and APC/C co-activator protein Cdc20), we reveal the molecular basis of MCC-mediated APC/C inhibition and the regulation of MCC assembly. The MCC inhibits the APC/C by obstructing degron recognition sites on Cdc20 (the substrate recruitment subunit of the APC/C) and displacing Cdc20 to disrupt formation of a bipartite D-box receptor with the APC/C subunit Apc10. Mad2, in the closed conformation (C-Mad2), stabilizes the complex by optimally positioning the Mad3 KEN-box degron to bind Cdc20. Mad3 and p31
comet
(also known as MAD2L1-binding protein) compete for the same C-Mad2 interface, which explains how p31
comet
disrupts MCC assembly to antagonize the SAC. This study shows how APC/C inhibition is coupled to degron recognition by co-activators.
The crystal structure of fission yeast mitotic checkpoint complex (MCC) reveals how MCC assembly is regulated and the molecular basis of anaphase-promoting complex (APC/C) inhibition by MCC.
Dividing the spoils in cell division
The equal distribution of duplicated chromosomes between the two daughter cells produced during mitosis depends on the activity of the spindle assembly checkpoint (SAC), which pauses the cell cycle until all sister chromatids have attached to the bipolar mitotic spindle. SAC function is exerted by the mitotic checkpoint complex (MCC). The crystal structure of MCC from fission yeast has now been determined, revealing the molecular basis of its interaction with anaphase-promoting complex, the ubiquitin ligase that initiates chromosome segregation. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0028-0836 1476-4687 |
DOI: | 10.1038/nature10896 |