Cyclin B1-Cdk1 binds MAD1 and facilitates its release from the nuclear pore complex to ensure a robust Spindle Assembly Checkpoint

How the cell rapidly and completely reorganises its architecture when it divides is a problem that has fascinated for almost 150 years. We now know that the core regulatory machinery is highly conserved in eukaryotes but how these multiple protein kinases, protein phosphatases, and ubiquitin ligases are coordinated in space and time to remodel the cell in a matter of minutes remains a major question. Cyclin B-Cdk is the primary kinase that drives mitotic remodelling and here we show that it is targeted to the nuclear pore complex (NPC) by binding an acidic face of the kinetochore checkpoint protein, MAD1, where it coordinates NPC disassembly with kinetochore assembly. This localised Cyclin B1-Cdk1 activity is needed for the proper release of MAD1 from the embrace of TPR at the nuclear pore so that it can be recruited to kinetochores before nuclear envelope breakdown to maintain genomic stability.