Part II: Controlling the Cell Cycle: Cdk Substrates
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Part 1: Cells reproduce by duplicating their chromosomes and other components and then distributing them into a pair of genetically identical daughter cells. This series of events is called the cell cycle. In the first part of this lecture, I provide a general overview of the cell-cycle control system, a complex regulatory network that guides the cell through the steps of cell division. I briefly describe the major components of this regulatory system and how they fit together to form a series of biochemical switches that trigger cell-cycle events at the correct time and in the correct order.
Part 2: Cyclin-dependent kinases (Cdks) are the central components of the control system that initiates the events of the cell cycle. In the second part of this lecture, I discuss my laboratory's efforts to address the problem of how the Cdks trigger cell-cycle events. I describe our methods for identifying the protein substrates of the Cdks, and I discuss how these studies have led to important clues about how Cdks find their correct targets in the cell and how phosphorylation of those targets governs their function.
Part 3: In the anaphase stage of the cell cycle, the duplicated chromosomes are pulled apart by a machine called the mitotic spindle, resulting in the distribution of a complete set of chromosomes to each of the daughter cells. In the third part of this lecture, I describe the combination of biochemistry and microscopy in my laboratory that led to the discovery of a regulatory switch that triggers the abrupt and synchronous separation of the chromosomes at the onset of anaphase.
David Morgan is a Professor in the Departments of Physiology and Biochemistry & Biophysics at the University of California, San Francisco (UCSF). He received an undergraduate degree in animal physiology from the University of Calgary in 1980, followed in 1986 by a PhD from UCSF, with Richard Roth.
Following postdoctoral studies with William Rutter and Harold Varmus at UCSF, he started his own laboratory there in 1990. His research interests are centered on the biochemical mechanisms and regulatory circuits that govern cell-cycle progression.
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Alberts B., Johnson A., Lewis J., Raff M., Roberts K., and Walter P. (2008) Molecular Biology of the Cell (5th edition), Chapter 17. New York: Garland Science.
Morgan D.O. (2007) The Cell Cycle: Principles of Control. London: New Science Press.
Holt, L.J., Krutchinsky, A.N., and Morgan, D.O. (2008) Positive feedback sharpens the anaphase switch. Nature 454, 353-357.
Holt, L.J., Tuch, B.B., Villén, J., Johnson, A.D., Gygi, S.P., and Morgan, D.O. (2009) Global analysis of Cdk1 phosphorylation sites provides insights into evolution. Science 325, 1682-1686.
Loog, M., and Morgan, D.O. (2005) Cyclin specificity in the phosphorylation of cyclin-dependent kinase substrates. Nature 434, 104-108.
Peters J.M. (2006) The anaphase promoting complex/cyclosome: a machine designed to destroy. Nat. Rev. Mol. Cell Biol. 7:644-656.
Sullivan, M., and Morgan, D.O. (2007) Finishing mitosis, one step at a time. Nat. Rev. Mol. Cell Biol. 8, 894-903.
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.