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Anaphase inactivation of the spindle checkpoint


Anaphase inactivation of the spindle checkpoint.

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The spindle checkpoint delays cell cycle progression until microtubules attach each pair of sister chromosomes to opposite poles of the mitotic spindle. Following sister chromatid separation, however, the checkpoint ignores chromosomes whose kinetochores are attached to only one spindle pole, a state that activates the checkpoint prior to metaphase. We demonstrate that, in budding yeast, mutual inhibition between the anaphase-promoting complex (APC) and Mps1, an essential component of the checkpoint, leads to sustained inactivation of the spindle checkpoint. Mps1 protein abundance decreases in anaphase, and Mps1 is a target of the APC. Furthermore, expression of Mps1 in anaphase, or repression of the APC in anaphase, reactivates the spindle checkpoint. This APC-Mps1 feedback circuit allows cells to irreversibly inactivate the checkpoint during anaphase.


Palframan WJ, Meehl JB, Jaspersen SL, Winey M, Murray AW

Science (New York, N.Y.)

2006-08-04 00:00

313

5787

680-4

Amino Acid Sequence,Anaphase,Cell Cycle Proteins,Chromosomes, Fungal,Feedback, Biochemical,GTP-Binding Proteins,Kinetochores,Mitosis,Mitotic Spindle Apparatus,Molecular Sequence Data,Nuclear Proteins,Phosphorylation,Protein-Serine-Threonine Kinases,Protein-Tyrosine Kinases,Recombinant Fusion Proteins,Saccharomyces cerevisiae,Saccharomyces cerevisiae Proteins,Ubiquitin-Protein Ligase Complexes,CDC15 protein,CDC20 protein, S cerevisiae,Cell Cycle Proteins,MAD1 protein, S cerevisiae,MAD2 protein, S cerevisiae,Nuclear Proteins,PDS1 protein, S cerevisiae,Recombinant Fusion Proteins,Saccharomyces cerevisiae Proteins,MPS1 protein, S cerevisiae,Protein-Tyrosine Kinases,Protein-Serine-Threonine Kinases,GTP-Binding Proteins,Ubiquitin-Protein Ligase Complexes,anaphase-promoting complex

Department of Molecular and Cellular Biology, Biological Laboratories, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA

Science

NIGMS GM43987, NIGMS GM51312

1095-9203

10.1126/science.1127205

1127205

1234

True

16825537

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