George S. Brush
George S. Brush, Ph.D.
Associate Director, Cancer Biology Graduate Program
421 E. Canfield Street, Suite 3122
Detroit, MI 48201
Mentoring: Layne Weatherford (Senior Student)
- DNA damage and recombination checkpoints
- Regulation of pre-meiotic DNA replication
- Transcription mechanisms in early meiosis
Members of the ATM family of protein kinases are central regulators of the DNA damage response in eukaryotic cells, serving to directly and indirectly control downstream targets that mediate cell cycle delay, apoptosis, and DNA repair. A defect in any one of these three processes greatly increases the risk of cancer development. One of the main goals of our research program is to define the molecular mechanisms underlying the function of ATM and related enzymes such as ATR. Because the DNA damage response pathways have been highly conserved through evolution, we have elected to study the experimentally tractable budding yeast Saccharomyces cerevisiae. A principal homologue of ATM and ATR in yeast is Mec1, required for multiple checkpoint-associated cell cycle delay responses and certain types of DNA repair. We are employing both genetic and biochemical methods to further understand 1) how the Mec1 protein kinase is activated and; 2) the consequences of this activation. Our recent studies have explored the role of Mec1 during meiosis and have led to a new project aimed at defining the means by which a meiotic cell commits to DNA replication and prevents DNA re-replication. We anticipate that these studies will provide fundamental insight into mechanisms that preserve genomic integrity during gamete development.
Brush GS, Najor NA, Dombkowski AA, Cukovic D, Sawarynski KE. Yeast IME2 functions early in meiosis upstream of cell cycle-regulated SBF and MBF targets. PLoS One. 2012;7:e31575
Brush, G.S., Najor, N.A. Keeping a good rep in meiosis: mind the CDK. Cell Cycle. 2009;8:1299-300.
Sawarynski, K.E., Najor, N.A. Kepsel, A.C., and Brush, G.S. Sic1-induced DNA re-replication during meiosis. Proc. Natl. Acad. Sci. USA. 2009;106:232-7.
Sawarynski, K.E., Kaplun, A., Tzivion, G., and Brush, G.S. Distinct activities of the related protein kinases Cdk1 and Ime2. Biochem. Biophys Acta. Mar;1773:450-6.
Bartrand, A.J., Iyasu, D., Marinco, S.M., and Brush, G.S. Evidence of meiotic crossover control in Saccharomyces cerevisiae through Mec1-mediated phosphorylation of replication protein A. Genetics. 2006;172:27-39.
Education and Training
PhD (1992): Johns Hopkins University, Baltimore, Maryland
Cancer Biology Courses Taught:
CB7210 Fundamentals of Cancer Biology
CB7220 Molecular Biology of Cancer Development
CB7240 Principles of Cancer Therapy
CB7300 Special Topics F31 Grant Writing Course
CB7700 Recent Developments in Cancer Biology
CB7990 Research Technologies in Cancer Biology (Course Director)