Leland H. Hartwell, Ph.D.
Professor of Genome Sciences
Adjunct Professor of Medicine
Fred Hutchinson Cancer Research Center
1100 Fairview Ave. N, D1-060
Seattle, WA 98109-1024
Phone: 206-667-5670
FAX: 206-667-5268
E-mail: lhartwel@fhcrc.org
Research Program:
Dr. Hartwell’s research program uses yeast genetics to study the control of the cell cycle by checkpoints, control circuits that arrest progression of the cell cycle when chromosomal damage is present. Two checkpoints are being investigated, one that controls mitosis in response to DNA double strand breaks and another that controls DNA replication in the presence of DNA alkylation damage. The Hartwell lab studies two aspects of yeast cell biology, the control of the cell cycle and the development of cell polarity. 1) The cell cycle is controlled in response to DNA damage and other perturbations by controls discovered in the Hartwell Lab, called checkpoints. Checkpoints arrest progress through the cell cycle so that damage can be repaired before the cell continues on. Checkpoints are responsible for the high fidelity of mitotic chromosome replication and segregation providing surveillance at the G1 to S transition, during S phase, and at the G2 to M transition. Loss of the G1 checkpoint in human cells is an important element in the generation of cancer cells since this loss unleashes an instability of the genome permitting rapid tumor cell evolution. 2) During mating, yeast cells polarize toward one another in response to pheromone signals. The Hartwell lab is investigating the functions needed for a cell to reorient its polarity in response to an external signal. They have found that a pheromone receptor and trimeric G protein play important roles. How the receptor communicates with the cell's cytoskeleton to direct polarity is an issue of central concern. The Hartwell group has also discovered that a yeast cell has two mating pathways, one that is used when pheromone gradients can be detected and another that the cell uses when the pheromone concentration saturates the cell's detection system. Another issue of current study is how the cell switches from one behavior to another. In both of these areas yeast genetics is exploited to identify the components that function in the process under consideration and to determine the particular role that a gene product plays.
Investigator: Dr. Hartwell is President and Director of the Fred Hutchinson Cancer Research Center and Professor of Genome Sciences at the University of Washington. He is a member of the National Academy of Sciences.
Representative Publications:
Weinert TA, Hartwell LH: The RAD9 gene controls the cell cycle response to DNA damage in Saccharomyces cerevisiae. Science 241: 317-322, 1988
Hartwell LH, Weinert T: Checkpoints: Controls that ensure the order of cell cycle events. Science 246: 629-634, 1989
Hartwell LH and Kastan MB: Cell cycle control and cancer. Science 266:1821-1828, 1994
Paulovich AG and Hartwell LH: A checkpoint regulates the rate of progression through S phase in S. cerevisiae in response to DNA damage. Cell 82:841-847, 1995
Toczyski DP, Galgoczy DJ, Hartwell LH: CDC5 and CKII control adaptation to the yeast DNA damage checkpoint. Cell 90:1097-1106, 1997
Hartwell LH, Szankasi P, Roberts CJ, Murray AW, Friend SH: Integrating genetic approaches into the discovery of anticancer drugs. Science 278:1064-1068, 1997.
Paulovich AG, Armour CD, Hartwell LH: The Saccharomyces cerevisiae RAD9, RAD17, RAD24 and MEC3 genes are required for tolerating irreparable, ultraviolet-induced DNA damage. Genetics 150:75-93, 1998.
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of Medical Genetics, University of Washington.
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Last updated: May 21, 2007 (content 1999)
