Jon Skotheim, "Cell Cycle Dynamics"

Jan Skotheim
Stanford University

"Cell Cycle Dynamics"

Abstract:  The G1 cell cycle checkpoint regulates commitment to cell division in response to multiple internal and external signals. Many molecular features of this checkpoint, known as Start in yeast and the restriction point in man, are conserved across eukaryotes.  My laboratory applies concepts from dynamical systems to investigate this crucial cellular decision. We have shown that commitment to cell division corresponds precisely to activation of a positive feedback loop of G1 cyclins. Furthermore, we demonstrated how differential chemical kinetics ensure that commitment to cell division precedes genome-wide changes in transcription. This 'feedback-first' regulation is a conserved feature of G1/S control across eukaryotes, and likely regulates other cellular and developmental transitions. Finally, we showed how feed-forward regulation of a cell cycle inhibitor balances the seemingly conflicting aims of stability and reversibility of a cellular state. Taken together, our work demonstrates the potency of integrating concepts from dynamical systems with genetic and biochemical analysis to understand the principles of checkpoint control.