Core Faculty

David O. Morgan, Ph.D.

Research Description

Cells reproduce by duplicating their genomes and other components and then distributing these components equally into two daughter cells. The carefully orchestrated series of events that leads to cell duplication and division is called the cell cycle. Cell-cycle events are timed and coordinated by a complex network of regulatory proteins called the cell-cycle control system.

We use a variety of biochemical and genetic approaches, primarily in the budding yeast Saccharomyces cerevisiae, to study the components and design of the eukaryotic cell-cycle control system. One of our central goals for many years has been to understand the structure, regulation, and functions of the cyclin-dependent kinases or Cdks, which serve as the highly conserved master regulators of cell-cycle events. Our work in this area has recently focused on the development of novel approaches to identify and characterize the substrates of Cdks, in collaboration with our UCSF colleague Kevan Shokat. Our identification of large numbers of Cdk targets has provided important insights into the poorly understood mechanisms by which Cdks control chromosome duplication in S phase and chromosome segregation in M phase.

Another major area of interest is the regulatory subsystem that coordinates the complex events underlying chromosome segregation in anaphase of mitosis. Our efforts focus primarily on a multisubunit ubiquitin-protein ligase called the Anaphase-Promoting Complex or APC. This remarkable enzyme initiates anaphase by catalyzing the formation of polyubiquitin chains on numerous mitotic regulators, thereby targeting them for destruction in the proteasome. We are using a wide range of approaches to dissect the function of the APC and to identify and characterize other regulatory molecules that work with the APC to determine the precise timing of APC target destruction in late mitosis.

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Selected Publications

Morgan, D.O. (2007) The Cell Cycle: Principles of Control. London: New Science Press.

Rodrigo-Brenni, M.C., and Morgan, D.O. (2007) Sequential E2s drive polyubiquitin chain assembly on APC targets. Cell, in press.

Holt, L.J., Hutti, J.E., Cantley, L.C., and Morgan, D.O. (2007) Evolution of Ime2 phosphorylation sites on Cdk1 substrates provides a mechanism to limit the effects of the phosphatase Cdc14 in meiosis. Mol. Cell 25, 689-702.

Woodbury, E.L., and Morgan, D.O. (2007) Cdk and APC activities limit the spindle-stabilizing function of Fin1 to anaphase. Nat. Cell Biol. 9, 106-112.

Loog, M., and Morgan, D.O. (2005) Cyclin specificity in the phosphorylation of cyclin-dependent kinase substrates. Nature 434, 104-108.

Ubersax, J.A., Woodbury, E.L., Quang, P.N., Paraz, M., Blethrow, J.D., Shah, K., Shokat, K.M., and Morgan, D.O. (2003) Targets of the cyclin-dependent kinase Cdk1. Nature, 425, 859-864.

Carroll, C.W., and Morgan, D.O. (2002) The Doc1 subunit is a processivity factor for the anaphase-promoting complex. Nat. Cell Biol. 4, 880-887.

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Contact Information

Email: david.morgan@ucsf.edu
Phone: 415-476-6695
Mailing Address:
UCSF Genentech Hall
Mailcode 2200, Rm N312B
600 16th Street
San Francisco, CA 94158-2517

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