Checkpoint Proteins Bub1 and Bub3 Delay Anaphase Onset in Response to Low Tension Independent of Microtubule-Kinetochore Detachment

Cell Rep. 2019 Apr 9;27(2):416-428.e4. doi: 10.1016/j.celrep.2019.03.027.

Abstract

The spindle assembly checkpoint (SAC) delays anaphase onset until sister chromosomes are bound to microtubules from opposite spindle poles. Only then can dynamic microtubules produce tension across sister kinetochores. The interdependence of kinetochore attachment and tension has proved challenging to understanding SAC mechanisms. Whether the SAC responds simply to kinetochore attachment or to tension status remains obscure. Unlike higher eukaryotes, budding yeast kinetochores bind only one microtubule, simplifying the relation between attachment and tension. We developed a Taxol-sensitive yeast model to reduce tension in fully assembled spindles. Our results show that low tension on bipolar-attached kinetochores delays anaphase onset, independent of detachment. The delay is transient relative to that imposed by unattached kinetochores. Furthermore, it is mediated by Bub1 and Bub3, but not Mad1, Mad2, and Mad3 (BubR1). Our results demonstrate that reduced tension delays anaphase onset via a signal that is temporally and mechanistically distinct from that produced by unattached kinetochores.

Keywords: kinetochore; microtubule; mitosis; spindle assembly checkpoint; taxol; tension.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anaphase / genetics*
  • Cell Cycle Proteins / genetics*
  • Humans
  • Kinetochores / metabolism*
  • Poly-ADP-Ribose Binding Proteins / genetics*
  • Protein-Serine-Threonine Kinases / genetics*

Substances

  • BUB3 protein, human
  • Cell Cycle Proteins
  • Poly-ADP-Ribose Binding Proteins
  • BUB1 protein, human
  • Protein-Serine-Threonine Kinases