Overview

• Sensors in live yeast cells detected cyclin-dependent kinase activity in the nucleus before any cytoplasmic activation, overturning the centrosome-first model of mitosis initiation.
• A substantial buildup of nuclear cyclin is required to trigger CDK activation, ensuring mitosis follows successful DNA replication and damage checkpoints.
• Once activated in the nucleus, cyclin-CDK complexes are exported into the cytoplasm where lower activation thresholds propagate downstream mitotic signals.
• Blocking cyclin export to cytoplasmic centrosomes prevents mitotic entry outside the nucleus despite nuclear CDK activation, highlighting the necessity of nucleocytoplasmic shuttling.
• Researchers believe this compartmentalized mechanism may be conserved in higher organisms, offering new directions for understanding human cell-cycle regulation.