The Cell Cycle

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Leland Hartwell's research in the UW genetics department on fundamental characteristics of the cell cycle of yeast may ultimately provide a key to understanding cancer as well.

The cell cycle refers to the processes by which cells grow and divide. Hartwell brought techniques of molecular genetics to bear on studies of the budding yeast, Saccharomyces cerevisiae, which shares with higher organisms—including humans—many common features of the way its cells reproduce. Hartwell's seminal studies of temperature-sensitive mutants (whose growth could be arrested at discrete points in the cycle) revealed how the complex array of cell cycle functions are coordinated.

Hartwell's studies led to the identification of some 50 Cell Division Cycle (CDC) genes, many of which are widely found in other eukaryotic cells and which exert critical control over the process of cell division. Predominant among these is CDC28, which encodes an enzyme that controls the progression of growth in cells from a certain stage to the next.

Thus, there are critical events that must take place in a stepwise manner in order for the cell cycle to proceed. Hartwell's recent studies on the RAD9 gene have confirmed the existence of "molecular checkpoints," that is, regulatory controls in the cell cycle that monitor whether an earlier event in the cycle has been satisfactorily completed.

Hartwell's work is providing important clues to the origin and behavior of cancer cells, which display defects in these checkpoint functions. Hartwell currently co-directs a major effort at the Fred Hutchinson Cancer Research Center in Seattle aimed at identifying drugs which directly perturb these crucial cell cycle controls in yeast. Major funding for this work is provided by the National Cancer Institute in the hope that the analogous cell cycle mechanisms in human cells may respond similarly to drugs identified in the program.

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