Ipl1p-dependent phosphorylation of Mad3p is required for the spindle checkpoint response to lack of tension at kinetochores

Emma M.J. King; Najma Rachidi; Nick Morrice; Kevin G. Hardwick; Michael J.R. Stark

doi:10.1101/gad.431507

Ipl1p-dependent phosphorylation of Mad3p is required for the spindle checkpoint response to lack of tension at kinetochores

¹ Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom;
² Division of Gene Regulation and Expression, College of Life Sciences, Medical Sciences Institute/Wellcome Trust Biocentre Complex, University of Dundee, Dundee DD1 5EH, United Kingdom;
³ Medical Research Council Protein Phosphorylation Unit, College of Life Sciences, Medical Sciences Institute/Wellcome Trust Biocentre Complex, University of Dundee, Dundee DD1 5EH, United Kingdom

↵6 These authors contributed equally to this work.

Abstract

The spindle checkpoint delays anaphase onset until all chromosomes are correctly attached to microtubules. Ipl1 protein kinase (Aurora B) is required to correct inappropriate kinetochore–microtubule attachments and for the response to lack of tension between sister kinetochores. Here we identify residues in the checkpoint protein Mad3p that are phosphorylated by Ipl1p. When phosphorylation of Mad3p at two sites is prevented, the cell’s response to reduced kinetochore tension is dramatically curtailed. Our data provide strong evidence for a distinct checkpoint pathway responding to lack of sister kinetochore tension, in which Ipl1p-dependent phosphorylation of Mad3p is a key step.

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Footnotes

↵4 Present addresses: Division of Gene Regulation and Expression, College of Life Sciences, Medical Sciences Institute/Wellcome Trust Biocentre Complex, University of Dundee, Dow Street, Dundee DD1 5EH, UK;
↵5 Paterson Institute for Cancer Research, Christie Hospital, Wilmslow Road, Withington, Manchester M20 4BX, UK.
↵7 Corresponding authors.

↵7 E-MAIL m.j.r.stark{at}dundee.ac.uk; FAX 44-1382-384782.
↵8 Kevin.Hardwick{at}ed.ac.uk; FAX 44-131-6507037.
Supplemental material is available at http://www.genesdev.org.
Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.431507
- Received March 2, 2007.
- Accepted March 19, 2007.
Freely available online through the Genes & Development Open Access option.