The internal Cdc20 binding site in BubR1 facilitates both spindle assembly checkpoint signalling and silencing

Research output: Contribution to journalJournal articleResearchpeer-review

  • Tiziana Lischetti
  • Gang Zhang
  • Garry G Sedgwick
  • Victor M Bolanos-Garcia
  • Nilsson, Jakob

Improperly attached kinetochores activate the spindle assembly checkpoint (SAC) and by an unknown mechanism catalyse the binding of two checkpoint proteins, Mad2 and BubR1, to Cdc20 forming the mitotic checkpoint complex (MCC). Here, to address the functional role of Cdc20 kinetochore localization in the SAC, we delineate the molecular details of its interaction with kinetochores. We find that BubR1 recruits the bulk of Cdc20 to kinetochores through its internal Cdc20 binding domain (IC20BD). We show that preventing Cdc20 kinetochore localization by removal of the IC20BD has a limited effect on the SAC because the IC20BD is also required for efficient SAC silencing. Indeed, the IC20BD can disrupt the MCC providing a mechanism for its role in SAC silencing. We thus uncover an unexpected dual function of the second Cdc20 binding site in BubR1 in promoting both efficient SAC signalling and SAC silencing.

Original languageEnglish
Article number5563
JournalNature Communications
Volume5
Pages (from-to)1-12
Number of pages12
ISSN2041-1723
DOIs
Publication statusPublished - Dec 2014

ID: 128722841