The segregation of sister chromatids during mitosis is one of the most easily visualized, yet most remarkable, events during the life cycle of a cell. The accuracy of this process is essential to maintain ploidy during cell duplication. Over the past 20 years, substantial progress has been made in identifying components of both the kinetochore and the mitotic spindle that generate the force to move mitotic chromosomes. Additionally, we now have a reasonable, albeit incomplete, understanding of the molecular and biochemical events that are involved in establishing and dissolving sister-chromatid cohesion. However, it is less well-understood how this dissolution of cohesion occurs synchronously on all chromosomes at the onset of anaphase. At the centre of the action is the anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase that, in association with its activator cell-division cycle protein 20 homologue (Cdc20), is responsible for the destruction of securin. This leads to the activation of separase, a specialized protease that cleaves the kleisin-subunit of the cohesin complex, to relieve cohesion between sister chromatids. APC/C–Cdc20 is also responsible for the destruction of cyclin B and therefore inactivation of the cyclin B–cyclin-dependent kinase 1 (Cdk1). This latter event induces a change in the microtubule dynamics that results in the movement of sister chromatids to spindle poles (anaphase A), spindle elongation (anaphase B) and the onset of cytokinesis. In the present paper, we review the emerging evidence that multiple, spatially and temporally regulated feedback loops ensure anaphase onset is rapid, co-ordinated and irreversible.
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February 2015
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Conference Article|
January 26 2015
Sharpening the anaphase switch
John C. Meadows;
John C. Meadows
*Division of Biomedical Cell Biology, Warwick Medical School, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, U.K.
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Jonathan B.A. Millar
Jonathan B.A. Millar
1
*Division of Biomedical Cell Biology, Warwick Medical School, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, U.K.
1To whom correspondence should be addressed (emailJ.Millar@warwick.ac.uk).
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Publisher: Portland Press Ltd
Received:
September 17 2014
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2015 Biochemical Society
2015
Biochem Soc Trans (2015) 43 (1): 19–22.
Article history
Received:
September 17 2014
Citation
John C. Meadows, Jonathan B.A. Millar; Sharpening the anaphase switch. Biochem Soc Trans 1 February 2015; 43 (1): 19–22. doi: https://doi.org/10.1042/BST20140250
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