Biological Sciences, Graduate Studies

		Mailing Address
		Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada, T6G 2E9 Office Number: G409 Bio Sciences Email address: lreha@gpu.srv.ualberta.ca Fax address: (780) 492-2216 Phone Number: (780) 492-5383 or 492-1109
Academic Degrees
	BSc (1971): University of Washington, degrees in Chemistry and Molecular Biology. PhD (1975): Johns Hopkins University, degree in Biochemistry from the Department of Biology.
Areas of Involvement
	Teaching
	Genetics 408/508 DNA Replication, Recombination, and Repair
	Professional Activities
	Canadian Society for Biochemistry, Molecular and Cell Biology American Society for Biochemistry and Molecular Biology Genetics Society of America American Chemical Society American Society for Microbiology
Current Research Interests
	Genetic, molecular, and biochemical approaches are used to study DNA polymerases and DNA replication. Bacteriophage T4 DNA polymerase has been developed into a model DNA polymerase. The T4 DNA polymerase and its accessory protein, gp45, are functional analogues of human pol delta and PCNA, respectively. T4 DNA polymerase also resembles several viral DNA polymerases including the DNA polymerases from herpes, vaccinia, and adeno viruses. The general research approach is to identify informative T4 DNA polymerase mutants by genetic selection and then to characterize the functionally distinct mutants biochemically. From these studies we are learning more about exonucleolytic proofreading, how DNA polymerases select correct nucleotides for incorporation, and how DNA polymerases become resistant to DNA polymerase inhibitors, which is important in understanding the action of antiviral drugs. Yeast is another excellent model system to study DNA replication. Genetic selection strategies are being developed to identify novel mutant DNA polymerases and the T4 DNA polymerase is being used as a guide to engineer informative yeast mutants. The yeast studies provide a bridge to studying DNA polymerases in cancer cells. In addition, we are using the information learned from our DNA polymerase studies to develop new DNA sequencing methods.
Selected Publications
	Hadjimarcou, M. I., Kokoska, R. J., Petes, T. D., and Reha-Krantz, L. J. (2001) Identification of a mutant DNA polymerase delta in Saccharomyces cerevisiae with an antimutator phenotype for frameshift mutations. Genetics 158, 177-186. Reha-Krantz, L. J. (2001) Reversion tests. Encyclopedia of Genetics, Editors-in-chief: S. Brenner and J. H. Miller, in press. Fidalgo da Silva, E., and Reha-Krantz, L. J. (2000) Dinucleotide repeat-expansion catalyzed by bacteriophage T4 DNA polymerase in vitro. J. Biol. Chem. 275, 31528-31535. Reha-Krantz, L. J., Marquez, L. A., Elisseeva, E., Baker, R. P., Bloom, L. B., Dunford, H. B., and Goodman, M. F. (1998) The proofreading pathway of bacteriophage T4 DNA polymerase. J. Biol. Chem. 273, 22969-22976. Beechem, J. M., Otto, M., Bloom, L B., Eritja, R., Reha-Krantz, L. J., and Goodman, M. F. (1998) Exonuclease/polymerase partitioning and equilibrium Mg²⁺ binding properties of bacteriophage T4 DNA polymerase. Biochemistry 37, 10144-10155. Baker, R. P., and Reha-Krantz, L. J. (1998) Identification of a transient excision intermediate at the crossroads between DNA polymerase extension and proofreading pathways. Proc. Natl. Acad. Sci. U.S.A. 95, 3507-3512. (Reviewed by Nature Sciences Update, April 23, 1998.) Stocki, S. A., Nonay, R. L., and Reha-Krantz, L. J. (1995) Dynamics of bacteriophage T4 DNA polymerase function: identification of amino acid residues which affect switching between polymerase and 3' —> 5' exonuclease activities. J. Mol. Biol. 254, 15-28.

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