A Clb/Cdk1-mediated regulation of Fkh2 synchronizes CLB expression in the budding yeast cell cycle

Abstract

Cell cycle control: Order in time achieved by dynamic coupling A dynamic coupling of cyclin-dependent kinase with transcription factors in yeast offers insights into the timely cell cycle progression. An international team lead by Matteo Barberis from University of Amsterdam in The Netherlands studied the molecular mechanisms responsible for the coordination of DNA replication with cell division. The researchers have demonstrated how the sequential order of waves of mitotic cyclins activating cyclin-dependent kinase, or Cdk, is achieved by synchronizing Cdk with transcriptional activities. They have generated a mathematical model that predicts a cyclin/Cdk-mediated regulation of an activator molecule to stimulate mitotic cyclin expression. This prediction was successfully validated experimentally, identifying Forkhead transcription factors, or Fkh, as pivotal molecules. Cyclin waves are temporally synchronized by Fkh, and a mitotic Clb/Cdk1-mediated regulation of Fkh modulates cyclin expression. The findings reveal a novel principle of design, with kinase and transcription activities interlocked to guarantee a timely cell cycle.