09 October 2017
The spindle assembly checkpoint (SAC) prevents premature sister chromatid separation during mitosis. Phosphorylation of unattached kinetochores by the Mps1 kinase promotes recruitment of SAC machinery that catalyzes assembly of the SAC effector mitotic checkpoint complex (MCC). The SAC protein Bub3 is a phospho-amino acid adaptor that forms structurally related stable complexes with functionally distinct paralogs named Bub1 and BubR1. A short motif (“loop”) of Bub1, but not the equivalent loop of BubR1, enhances binding of Bub3 to kinetochore phospho-targets. Here, we asked whether the BubR1 loop directs Bub3 to different phospho-targets. The BubR1 loop is essential for SAC function and cannot be removed or replaced with the Bub1 loop. BubR1 loop mutants bind Bub3 and are normally incorporated in MCC in vitro but have reduced ability to inhibit the MCC target anaphase-promoting complex (APC/C), suggesting that BubR1:Bub3 recognition and inhibition of APC/C requires phosphorylation. Thus, small sequence differences in Bub1 and BubR1 direct Bub3 to different phosphorylated targets in the SAC signaling cascade.
The molecular basis of kinetochore recruitment of Bub1 and BubR1 is dissected
Bub1 and BubR1 modulate the ability of Bub3 to recognize phosphorylated targets
A newly identified BubR1 motif targets Bub3 to the anaphase-promoting complex
The newly identified motif of BubR1 is required for checkpoint signaling
In spindle assembly checkpoint (SAC) signaling, the phospho-amino acid adaptor Bub3 forms complexes with Bub1 and BubR1 paralogs. Whether Bub3-Bub1 and Bub3-BubR1 bind distinct targets has been unclear. Overlack et al. demonstrate that this is the case and identify a motif in BubR1 that directs Bub3 to the SAC target, the anaphase-promoting complex.