Sensing chromosome bi-orientation by spatial separation of Aurora B kinase from kinetochore substrates

Dan Liu, Gerben Vader, Martijn J.M. Vromans, Michael A. Lampson, Susanne M.A. Lens

Research output: Contribution to journalArticleAcademicpeer-review

425 Citations (Scopus)

Abstract

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 bi-oriented attachments, but how physical forces are translated into signaling at individual centromeres is unknown. Using fluorescence resonance energy transfer-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 bi-oriented 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.

Original languageEnglish
Pages (from-to)1350-1353
Number of pages4
JournalScience
Volume323
Issue number5919
DOIs
Publication statusPublished - 18 Mar 2009
Externally publishedYes

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