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Determinants of robustness in spindle assembly checkpoint signalling

Heinrich, S., Geissen, E-M., Kamenz, J., Trautmann, S., Widmer, C., Drewe, P., Knop, M., Radde, N., Hasenauer, J. & Hauf, S., 27-Oct-2013, In : Nature Cell Biology. 15, p. 1328-1339 12 p.

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  • Determinants of robustness in spindle assembly checkpoint signalling

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DOI

  • Stephanie Heinrich
  • Eva-Maria Geissen
  • Julia Kamenz
  • Susanne Trautmann
  • Christian Widmer
  • Philipp Drewe
  • Michael Knop
  • Nicole Radde
  • Jan Hasenauer
  • Silke Hauf
The spindle assembly checkpoint is a conserved signalling pathway that protects genome integrity. Given its central importance, this checkpoint should withstand stochastic fluctuations and environmental perturbations, but the extent of and mechanisms underlying its robustness remain unknown. We probed spindle assembly checkpoint signalling by modulating checkpoint protein abundance and nutrient conditions in fission yeast. For core checkpoint proteins, a mere 20% reduction can suffice to impair signalling, revealing a surprising fragility. Quantification of protein abundance in single cells showed little variability (noise) of critical proteins, explaining why the checkpoint normally functions reliably. Checkpoint-mediated stoichiometric inhibition of the anaphase activator Cdc20 (Slp1 in Schizosaccharomyces pombe) can account for the tolerance towards small fluctuations in protein abundance and explains our observation that some perturbations lead to non-genetic variation in the checkpoint response. Our work highlights low gene expression noise as an important determinant of reliable checkpoint signalling.
Original languageEnglish
Pages (from-to)1328-1339
Number of pages12
JournalNature Cell Biology
Volume15
Publication statusPublished - 27-Oct-2013
Externally publishedYes

ID: 133224633