Letter abstract
Nature Cell Biology 9, 556 - 564 (2007)
Published online: 8 April 2007 | doi:10.1038/ncb1569
A functional genomic screen identifies a role for TAO1 kinase in spindle-checkpoint signalling
Viji M. Draviam1,5, Frank Stegmeier2,5, Grzegorz Nalepa3, Mathew E. Sowa3, Jing Chen3, Anthony Liang2, Gregory J. Hannon4, Peter K. Sorger1, J. Wade Harper3 & Stephen J. Elledge2
Defects in chromosome–microtubule attachment trigger spindle-checkpoint activation and delay mitotic progression1, 2. How microtubule attachment is sensed and integrated into the steps of checkpoint-signal amplification is poorly understood. In a functional genomic screen targeting human kinases and phosphatases, we identified a microtubule affinity-regulating kinase kinase, TAO1 (also known as MARKK) as an important regulator of mitotic progression, required for both chromosome congression and checkpoint-induced anaphase delay. TAO1 interacts with the checkpoint kinase BubR1 and promotes enrichment of the checkpoint protein Mad2 at sites of defective attachment, providing evidence for a regulatory step that precedes the proposed Mad2–Mad1 dependent checkpoint-signal amplification step3. We propose that the dual functions of TAO1 in regulating microtubule dynamics and checkpoint signalling may help to coordinate the establishment and monitoring of correct congression of chromosomes, thereby protecting genomic stability in human cells.
- Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
- Howard Hughes Medical Institute, Department of Genetics, Harvard Partners Center for Genetics and Genomics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
- Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
- Cold Spring Harbor Laboratory, Watson School of Biological Sciences, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
- These authors contributed equally to this work.
Correspondence to: Stephen J. Elledge2 e-mail: selledge@genetics.med.harvard.edu
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