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Lookup NU author(s): Dr Brian Ward,
Emeritus Professor Michael Whitaker,
Dr Jun-yong Huang
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The spindle assembly checkpoint (SAC) delays the metaphase to anaphase transition in response to lack of kinetochore-microtubule attachment and tension, until bipolar attachment of all chromosomes has been achieved. Kinetochore dynamic checkpoint proteins including Cdc20, Mad2 and BubR1 (along with Bub3), are the key components of a mitotic checkpoint complex (MCC), which inhibits activation of the Anaphase Promoting Complex/Cyclosome (APC/C) to prevent cell progression until the checkpoint is satisfied. Although it is hypothesised that the sequential formation of this mitotic checkpoint inhibitory complex is the mechanism by which the activity of Cdc20 (as the activator of the APC/C) is sequestered, the necessary conditions for the formation of the MCC remains subject to speculation. This includes aspects such as the order of formation and direct requirement of the kinetochore in protein-protein interactions. With the apparent recruitment of key checkpoint proteins upon checkpoint activation, clearly the kinetochore plays an important role. Recent studies suggest that unattached kinetochores not only catalyze the production of the MCC, but may also amplify Cdc20 inhibition and initiate the inhibition of Cdc20 which is already bound to APC/C. But with MCC found to be present outside of metaphase in HeLa cells, and complex formation in yeast previously shown to be independent of intact kinetochores, it could be argued that direct kinetochore interaction may not always be required as the template for the generation of this complex. Using Drosophila as model, we hope to expand upon current knowledge of the requirements involved in the interactions between key MCC proteins, by looking at how the SAC may be affected should the activity/behaviour of components of the MCC be disrupted.
Author(s): Herriott A, Whitaker M, Huang JY
Publication type: Conference Proceedings (inc. Abstract)
Publication status: Published
Conference Name: Meeting on The Cell Cycle
Year of Conference: 2010
Publisher: National Cancer Institute
Sponsor(s): National Cancer Institute, a branch of the National Institutes of Health.
Bristol-Myers Squibb Company
Hoffmann-La Roche Inc.
Life Technologies (Invitrogen & Applied Biosystems)
Merck (Schering-Plough) Research Laboratories
New England BioLabs, Inc.
OSI Pharmaceuticals, Inc.