Bub3p facilitates spindle checkpoint silencing in fission yeast.
Although critical for spindle checkpoint signaling, the role kinetochores play in anaphase promoting complex (APC) inhibition remains unclear. Here we show that spindle checkpoint proteins are severely depleted from unattached kinetochores in fission yeast cells lacking Bub3p. Surprisingly, a robust mitotic arrest is maintained in the majority of bub3 Delta cells, yet they die, suggesting that Bub3p is essential for successful checkpoint recovery. During recovery, two defects are observed: (1) cells mis-segregate chromosomes and (2) anaphase onset is significantly delayed. We show that Bub3p is required to activate the APC upon inhibition of Aurora kinase activity in checkpoint-arrested cells, suggesting that Bub3p is required for efficient checkpoint silencing downstream of Aurora kinase. Together, these results suggest that spindle checkpoint signals can be amplified in the nucleoplasm, yet kinetochore localization of spindle checkpoint components is required for proper recovery from a spindle checkpoint-dependent arrest.
Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, EH9 3JR, United Kingdom. vvanoost@staffmail.ed.ac.uk
Vincent
V
Vanoosthuyse
John C
JC
Meadows
Sjaak J A
SJ
van der Sar
Jonathan B A
JB
Millar
Kevin G
KG
Hardwick
D000705:Anaphase; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D020090:Chromosome Segregation / Q000235:genetics; D018386:Kinetochores / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D012568:Schizosaccharomyces / Q000166:cytology* / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism*
C544653:Bub3 protein, S pombe; D018797:Cell Cycle Proteins; D029702:Schizosaccharomyces pombe Proteins