Control of Cell Cycle Events by Cyclin-Dependent Kinases

University Of California Santa Cruz, Santa Cruz CA

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Abstract

The goal of our research is to understand the molecular mechanisms that determine cell size and coordinate cell growth with the cell cycle. Each cell type is characterized by a unique size and shape, and the control of cell growth is therefore integral to cellular form, function, and identity. It is likely that cell growth is controlled by highly intricate mechanisms, since single-celled organisms can maintain the same size and shape over widely varying growth conditions, and multicellular organisms are composed of cells of widely differing size and shape. Genetic experiments in both budding yeast and fission yeast have demonstrated that cyclin-dependent kinases play a critical role in controlling cell growth; however, the molecular mechanisms by which they do so have remained completely unknown. In budding yeast, inactivation of mitotic cyclin-dependent kinases results in continuous polarized cell growth during a G2/M arrest, causing the formation of highly elongated cells. The elongated cells grow significantly larger than wild type cells, indicating a severe failure in the mechanisms that control cell size and cell growth. Work from our lab and others has demonstrated that an intricate signaling network is also required for proper control of cell growth during G2/M. Genetic data argue that this signaling network controls Swe1, the budding yeast homolog of the Wee1 kinase, which is known to play a central role in coordinating cell growth and mitosis in fission yeast. Our most recent work suggests that Swe1 associates directly with mitotic cyclin-dependent kinase complexes and with proteins involved in cell growth, providing the first clues to the long mysterious molecular mechanisms that coordinate cell growth with the cell cycle. The focus of our future work will be to use biochemical approaches to identify and characterize multiprotein complexes that function in the molecular signaling mechanisms that coordinate cell growth and cell division.