A cyclin-polarity feedback network ensures healthy cell proliferation

Abstract

Abstract Healthy proliferation requires the coordination of cell cycle progression with cell polarity. In budding yeast, polarity is established when G1-cyclin-Cdc28 Cdk1 triggers Cdc42 activation to generate a cell pole that is used as an axis for growth and division. While polarity defects delay the cell cycle temporally, permitting error correction, it is unknown if Cdc28 Cdk1 directly rectifies errant polarity. Here, we identify an adaptive response where G1-cyclin-Cdc28 Cdk1 participates in error correction via the augmentation of its kinase activity towards substrates that activate Cdc42. The response involves temporal and spatial cell cycle reconfiguration via extended G1 cyclin expression, nucleocytoplasmic rerouting and signaling. However, this strategy has a cost: if the defect is irreparable, high G1-cyclin levels enforce inexorable cell cycle commitment in the absence of a daughter cell, generating multinucleate cells. G1-cyclins therefore not only trigger G1 events, but also monitor their execution, employing feedback to coordinate polarity with cell cycle progression.