Spatial control of the APC/C ensures the rapid degradation of Cyclin B1

The proper control of mitosis depends on the ubiquitin-mediated degradation of the right protein at the right time. This is effected by the Anaphase Promoting Complex/Cyclosome (APC/C) ubiquitin ligase that is regulated by the Spindle Assembly Checkpoint (SAC). The SAC prevents the APC/C from recognising CyclinB1 until all chromosomes are attached to the spindle, after which CyclinB1 is rapidly degraded to enable chromosome segregation and cytokinesis. We have a good understanding of how the SAC inhibits the APC/C, but relatively little is known about how the APC/C recognises CyclinB1 as soon as the SAC is turned off. Here, we show that the rapid recognition of Cyclin B1 requires spatial regulation of the APC/C. We find that CyclinB1 and the APC/C primarily interact at the mitotic apparatus because Cyclin B1 and the APC/C bind to nucleosomes through 'arginine-anchor' motifs. Mutating the arginine anchor on Cyclin B1 delays its degradation and cells become aneuploid. Our data demonstrate that mitotic chromosomes promote the efficient interaction between CyclinB1 and APC/C to ensure genomic stability.