KNL1/Spc105 recruits PP1 to silence the spindle assembly checkpoint

Curr Biol. 2011 Jun 7;21(11):942-7. doi: 10.1016/j.cub.2011.04.011.


The spindle assembly checkpoint (SAC) delays anaphase onset until kinetochores accomplish bioriented microtubule attachments [1]. Although several centromeric and kinetochore kinases, including Aurora B, regulate kinetochore-microtubule attachment and/or SAC activation [2-4], the molecular mechanism that translates bioriented attachment into SAC silencing remains unclear [5]. Employing a method to rapidly induce exact gene replacement in budding yeast [6], we show here that the binding of protein phosphatase 1 (PP1/Glc7) to the evolutionarily conserved RVSF motif of the kinetochore protein Spc105 (KNL1/Blinkin/CASC5) is essential for viability by silencing the SAC, while it plays an auxiliary nonessential role for physical chromosome segregation. Although Aurora B may inhibit this binding, persistent PP1-Spc105 interaction does not affect chromosome segregation and is insufficient to silence the SAC in the absence of microtubules, indicating that dynamic regulation of this interaction is dispensable. However, the amount of PP1 targeted to kinetochores must be finely tuned, because recruitment of either no or one extra copy of PP1 to Spc105 is detrimental, illustrating the vital impact of targeting an exiguous fraction of PP1 to the kinetochore. We propose that the PP1-Spc105 interaction enables local regulation of dynamic phosphorylation and dephosphorylation at the kinetochore to couple microtubule attachment and SAC silencing.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anaphase
  • Conserved Sequence
  • Genotype
  • Kinetochores / metabolism
  • Microtubule-Associated Proteins / chemistry
  • Microtubule-Associated Proteins / metabolism
  • Microtubule-Associated Proteins / physiology*
  • Mitosis / genetics
  • Mitosis / physiology
  • Mutagenesis, Site-Directed
  • Phosphorylation
  • Protein Phosphatase 1 / genetics
  • Protein Phosphatase 1 / metabolism
  • Protein Phosphatase 1 / physiology*
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / physiology*
  • Spindle Apparatus / metabolism*


  • Microtubule-Associated Proteins
  • Saccharomyces cerevisiae Proteins
  • Spc105 protein, S cerevisiae
  • GLC7 protein, S cerevisiae
  • Protein Phosphatase 1