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The 'anaphase problem': how to disable the mitotic checkpoint when sisters split.
María Dolores Vázquez-Novelle1, Lesia Mirchenko, Frank Uhlmann
1Cell Division and Aneuploidy Laboratory, Cancer Research UK, London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, UK.
Biochemical Society Transactions
|December 2, 2010
Summary
Eukaryotic cells prevent catastrophic errors during cell division by inactivating the mitotic checkpoint at anaphase onset. This ensures proper chromosome segregation by disabling the checkpoint when sister chromatids split.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Chromosome segregation fidelity is crucial for eukaryotic cell division.
- The mitotic checkpoint and error correction mechanisms safeguard this process.
- Aurora B kinase plays a key role in both pathways.
Purpose of the Study:
- To investigate how eukaryotic cells prevent the mitotic checkpoint from activating inappropriately at anaphase onset.
- To understand the 'anaphase problem' of disabling the checkpoint when sister chromatids split.
Main Methods:
- Review of recent research on mitotic checkpoint control.
- Analysis of the role of Cdk1 phosphorylation of INCENP.
- Examination of chromosomal passenger complex (CPC) dynamics.
Main Results:
- Disjunction of sister chromatids can trigger the mitotic checkpoint and error correction.
- Checkpoint inactivation at the metaphase-to-anaphase transition is essential.
- Reversal of Cdk1 phosphorylation of INCENP causes CPC relocation, contributing to inactivation.
Conclusions:
- Mitotic checkpoint inactivation at anaphase onset prevents re-engagement when sister chromatids split.
- The checkpoint remains responsive to tension loss even when satisfied.
- Understanding these mechanisms is key to controlling cell division fidelity.
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At the onset of anaphase, separase, a proteolytic enzyme, is...
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02:19The Spindle Assembly Checkpoint
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02:20Cohesins
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