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Published Online January 15, 2009
Science DOI: 10.1126/science.1167000

Reports

Submitted on October 9, 2008
Accepted on January 6, 2009

Sensing Chromosome Bi-Orientation by Spatial Separation of Aurora B Kinase from Kinetochore Substrates

Dan Liu 1, Gerben Vader 2, Martijn J. M. Vromans 3, Michael A. Lampson 1{dagger}*, Susanne M. A. Lens 3{dagger}

1 Department of Biology, University of Pennsylvania, Philadelphia, PA, USA.
2 Department of Medical Oncology, University Medical Center, Utrecht, Netherlands.; Present address: Whitehead Institute for Biomedical Research, Cambridge, MA, USA.
3 Department of Medical Oncology, University Medical Center, Utrecht, Netherlands.

* To whom correspondence should be addressed.
Michael A. Lampson , E-mail: lampson{at}sas.upenn.edu

{dagger}These authors contributed equally to this work.

Successful cell division requires that chromosomes attach to opposite poles of the mitotic spindle (bi–orientation). Aurora B kinase regulates chromosome–spindle attachments by phosphorylating kinetochore substrates that bind microtubules. Centromere tension stabilizes bioriented attachments, but how physical forces are translated into signaling at individual centromeres is unknown. Using fluorescence resonance energy transfer (FRET)—based biosensors to measure localized phosphorylation dynamics in living cells, we found that phosphorylation of an Aurora B substrate at the kinetochore depended on its distance from the kinase at the inner centromere. Furthermore, repositioning Aurora B closer to the kinetochore prevented stabilization of bioriented attachments and activated the spindle checkpoint. Thus, centromere tension can be sensed by increased spatial separation of Aurora B from kinetochore substrates, which reduces phosphorylation and stabilizes kinetochore microtubules.


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