A Novel Protein Phosphatase 1-Dependent Spindle Checkpoint Silencing Mechanism

Hardwic lab paper featured in Current Biology.

Authors

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Image from Hardwick paper, Current Biology 2009

Vanoosthuyse V, Hardwick KG.

Curr Biol. 2009 Jul 8.(epublished ahead of print)

Summary

The spindle checkpoint is a surveillance system acting in mitosis to delay anaphase onset until all chromosomes are properly attached to the mitotic spindle.  Several protein kinases have critical roles to play in spindle checkpoint signalling, but the mechanism(s) by which they inhibit mitotic progression remains unclear. Furthermore, it is not known whether their activity needs to be reversed by protein phosphatases before anaphase onset can occur. Here we employ fission yeast to show that Aurora (Ark1) kinase activity is directly required to maintain a spindle checkpoint arrest, even in the presence of many unattached kinetochores. Upon Ark1 inhibition, checkpoint complexes are disassembled and cyclin B is rapidly degraded. Importantly, this checkpoint silencing requires the kinetochore-localised isoform of protein phosphatase 1 (PP1Dis2). We propose that PP1Dis2-mediated dephosphorylation of checkpoint components forms a novel spindle checkpoint silencing mechanism.

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Article in Cell