Two closely connected mechanisms safeguard the fidelity of chromosome segregation in eukaryotic cells. The mitotic checkpoint monitors the attachment of kinetochores to microtubules and delays anaphase onset until all sister kinetochores have become attached to opposite poles. In addition, an error correction mechanism destabilizes erroneous attachments that do not lead to tension at sister kinetochores. Aurora B kinase, the catalytic subunit of the CPC (chromosomal passenger complex), acts as a sensor and effector in both pathways. In this review we focus on a poorly understood but important aspect of mitotic control: what prevents the mitotic checkpoint from springing into action when sister centromeres are split and tension is suddenly lost at anaphase onset? Recent work has shown that disjunction of sister chromatids, in principle, engages the mitotic checkpoint, and probably also the error correction mechanism, with potentially catastrophic consequences for cell division. Eukaryotic cells have solved this ‘anaphase problem’ by disabling the mitotic checkpoint at the metaphase-to-anaphase transition. Checkpoint inactivation is in part due to the reversal of Cdk1 (cyclin-dependent kinase 1) phosphorylation of the CPC component INCENP (inner centromere protein; Sli15 in budding yeast), which causes the relocation of the CPC from centromeres to the spindle midzone. These findings highlight principles of mitotic checkpoint control: when bipolar chromosome attachment is reached in mitosis, the checkpoint is satisfied, but still active and responsive to loss of tension. Mitotic checkpoint inactivation at anaphase onset is required to prevent checkpoint re-engagement when sister chromatids split.
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Conference Article|
November 24 2010
The ‘anaphase problem’: how to disable the mitotic checkpoint when sisters split
María Dolores Vázquez-Novelle;
María Dolores Vázquez-Novelle
*Cell Division and Aneuploidy Laboratory, Cancer Research UK, London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, U.K.
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Lesia Mirchenko;
Lesia Mirchenko
†Chromosome Segregation Laboratory, Cancer Research UK, London Research Institutes, 44 Lincoln's Inn Fields, London WC2A 3PX, U.K.
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Frank Uhlmann;
Frank Uhlmann
1
†Chromosome Segregation Laboratory, Cancer Research UK, London Research Institutes, 44 Lincoln's Inn Fields, London WC2A 3PX, U.K.
1Correspondence may be addressed to either of these authors (email frank.uhlmann@cancer.org.uk or mark.petronczki@cancer.org.uk).
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Mark Petronczki
Mark Petronczki
1
*Cell Division and Aneuploidy Laboratory, Cancer Research UK, London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, U.K.
1Correspondence may be addressed to either of these authors (email frank.uhlmann@cancer.org.uk or mark.petronczki@cancer.org.uk).
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Publisher: Portland Press Ltd
Received:
July 27 2010
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2010 Biochemical Society
2010
Biochem Soc Trans (2010) 38 (6): 1660–1666.
Article history
Received:
July 27 2010
Citation
María Dolores Vázquez-Novelle, Lesia Mirchenko, Frank Uhlmann, Mark Petronczki; The ‘anaphase problem’: how to disable the mitotic checkpoint when sisters split. Biochem Soc Trans 1 December 2010; 38 (6): 1660–1666. doi: https://doi.org/10.1042/BST0381660
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