biostudies-literature00490Liu DDutch Research Council (NWO)NIGMS NIH HHS1350-3https://www.ebi.ac.uk/biostudies/studies/S-EPMC2713345biostudies-literatureUnknown323(5919)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.Science (New York, N.Y.)Sensing chromosome bi-orientation by spatial separation of aurora B kinase from kinetochore substrates.PMC2713345917.66.332GM083988R01 GM083988-01R01 GM083988Vader GVromans MJLens SMLampson MALiu D49falseSensing chromosome bi-orientation by spatial separation of aurora B kinase from kinetochore substrates.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.2009-01-01T00:00:00Z2009 Mar2024-11-20T10:56:35.846Z2019-03-27T00:23:39ZS-EPMC27133451915080810.1126/science.1167000