The Spindle Assembly Checkpoint works like a rheostat not a toggle-switch

The Spindle Assembly Checkpoint works like a rheostat not a toggle-switch

The Spindle Assembly Checkpoint (SAC) is essential in mammalian mitosis to ensure the equal segregation of sister chromatids1, 2. The SAC generates a Mitotic Checkpoint Complex (MCC) to prevent the Anaphase Promoting Complex/Cyclosome (APC/C) from targeting key mitotic regulators for destruction unt...

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Main Authors: Collin, Philippe, Nashchekina, Oxana, Walker, Rachael, Pines, Jonathon
Format: Online
Language:English
Published: 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836401/
id pubmed-3836401
recordtype oai_dc
spelling pubmed-38364012014-05-01 The Spindle Assembly Checkpoint works like a rheostat not a toggle-switch Collin, Philippe Nashchekina, Oxana Walker, Rachael Pines, Jonathon Article The Spindle Assembly Checkpoint (SAC) is essential in mammalian mitosis to ensure the equal segregation of sister chromatids1, 2. The SAC generates a Mitotic Checkpoint Complex (MCC) to prevent the Anaphase Promoting Complex/Cyclosome (APC/C) from targeting key mitotic regulators for destruction until all the chromosomes have attached to the mitotic apparatus1, 3, 4. A single unattached kinetochore can delay anaphase for several hours5, but how it is able to block the APC/C throughout the cell is not understood. Current concepts of the SAC posit that it exhibits either an ‘all or nothing’ response6 or there is a minimum threshold sufficient to block the APC/C7. Here, we have used gene targeting to measure SAC activity and find that it does not have an ‘all or nothing’ response. Instead, the strength of the SAC depends on the amount of Mad2 recruited to kinetochores and on the amount of MCC formed. Furthermore, we show that different drugs activate the SAC to different extents, which may be relevant to their efficacy in chemotherapy. 2013-10-06 2013-11 /pmc/articles/PMC3836401/ /pubmed/24096242 http://dx.doi.org/10.1038/ncb2855 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Collin, Philippe
Nashchekina, Oxana
Walker, Rachael
Pines, Jonathon
spellingShingle Collin, Philippe
Nashchekina, Oxana
Walker, Rachael
Pines, Jonathon
The Spindle Assembly Checkpoint works like a rheostat not a toggle-switch
author_facet Collin, Philippe
Nashchekina, Oxana
Walker, Rachael
Pines, Jonathon
author_sort Collin, Philippe
title The Spindle Assembly Checkpoint works like a rheostat not a toggle-switch
title_short The Spindle Assembly Checkpoint works like a rheostat not a toggle-switch
title_full The Spindle Assembly Checkpoint works like a rheostat not a toggle-switch
title_fullStr The Spindle Assembly Checkpoint works like a rheostat not a toggle-switch
title_full_unstemmed The Spindle Assembly Checkpoint works like a rheostat not a toggle-switch
title_sort spindle assembly checkpoint works like a rheostat not a toggle-switch
description The Spindle Assembly Checkpoint (SAC) is essential in mammalian mitosis to ensure the equal segregation of sister chromatids1, 2. The SAC generates a Mitotic Checkpoint Complex (MCC) to prevent the Anaphase Promoting Complex/Cyclosome (APC/C) from targeting key mitotic regulators for destruction until all the chromosomes have attached to the mitotic apparatus1, 3, 4. A single unattached kinetochore can delay anaphase for several hours5, but how it is able to block the APC/C throughout the cell is not understood. Current concepts of the SAC posit that it exhibits either an ‘all or nothing’ response6 or there is a minimum threshold sufficient to block the APC/C7. Here, we have used gene targeting to measure SAC activity and find that it does not have an ‘all or nothing’ response. Instead, the strength of the SAC depends on the amount of Mad2 recruited to kinetochores and on the amount of MCC formed. Furthermore, we show that different drugs activate the SAC to different extents, which may be relevant to their efficacy in chemotherapy.
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836401/
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