Mechanisms and Control of Cell Cycle Checkpoints

Professor Baltazar Aguda, Laurentian University, Canada, Department of Chemistry and Biochemistry

A consensus view of the regulatory mechanism of the mammalian cell cycle will be described, focusing on G1 and G2 checkpoints. The G1 checkpoint, called the restriction point, marks the transition between mitogen-dependent and mitogen-independent cell cycle progression; the G2 checkpoint will be discussed in relation with DNA damage signal transduction pathways that arrest or slow down the cell cycle before mitosis. An elementary stability analysis of the steady states of coupled phosphorylation-dephosphorylation (PD) cycles suggests the following core components of the switching dynamics at each of these checkpoints: (1) a positive coupling between two PD cycles and (2) a mutually antagonistic interaction between one of these cycles and another protein. Outstanding issues and problems in cell cycle modeling will be mentioned briefly.