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Kristina H. Schmidt, Ph.D. E-mail:
kschmidt@cas.usf.edu |
Training
M.Sc., University of Leipzig (Germany), 1995
Ph.D., University of Edinburgh (UK), 1999
Postdoctoral Fellow, Ludwig Institute for Cancer Research, UC-San Diego, 1999-2005
Research
Interests
The main goal of my laboratory is to obtain a better understanding of how eukaryotic cells preserve the integrity of their genome. Genetic studies of the yeast Saccharomyces cerevisiae have implicated numerous genes in the maintenance of genome stability, including those that function in cell cycle checkpoints, DNA replication, mismatch repair, recombination, oxidant defense mechanisms and telomere maintenance. Cells with defects in these pathways can accumulate point mutations, frameshifts and/or gross-chromosomal rearrangements, i.e. translocations, chromosome fusions, large interstitial deletions or terminal deletions of chromosome arms that are healed by de novo telomere additions.
We are particularly interested in S. cerevisiae proteins that function at the interface between DNA replication and DNA repair, such as the non-replicative DNA helicases Sgs1, Rrm3 and Srs2. Cells with mutations in any one of these DNA helicases grow normally and exhibit low to moderate levels of genome instability, whereas mutations in any two of these DNA helicases lead to a severe, slow-growth phenotype that can be suppressed by disrupting homologous recombination. This suggests the accumulation of recombination-dependent DNA structures that cannot be accurately resolved and become toxic to the cell. Current work in the lab utilizes a wide range of genetical and biochemical techniques to investigate how these DNA helicases and interacting proteins may aid replication fork progression, prevent the initiation of aberrant recombination events and suppress chromosomal rearrangements.
S. cerevisiae is genetically and biochemically well characterized and its genome is fully sequenced and annotated. Its excellent genetics and ease of manipulation make it one of the most powerful model organisms for the study of evolutionarily highly conserved DNA metabolic pathways. Many of the genes being studied in my laboratory have human homologues, of which some are known to be involved in genetic diseases. Thus, insights gained from our investigations may shed light on the causes of genome instability in human cells, cancer predisposition and aging.
Search
for publications by: 
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search will be conducted at the US National Library of Medicine (NLM) and PubMed.
Selected
Publications
Schmidt KH, Wu J, and Kolodner RD. (2006) Control of translocations between highly diverged genes by Sgs1, the Saccharomyces cerevisiae homolog of the Bloom's syndrome gene. Mol. Cell. Biol. 26(14):5406-5420.
Schmidt KH, Pennaneach V, Putnam CD and Kolodner RD. (2006) Analysis of gross-chromosomal rearrangements in Saccharomyces cerevisiae. Methods Enzymol. 409:462-76.
Schmidt KH, and Kolodner RD. (2004) Requirement of Rrm3 helicase for repair of spontaneous DNA lesions in cells lacking Srs2 or Sgs1 helicase. Mol Cell Biol. 24(8):3213-26.
Schmidt KH, Derry K, and Kolodner RD. (2002) Rrm3 of Saccharomyces cerevisiae, a 5’ to 3’ DNA helicase, interacts physically with proliferating cell nuclear antigen (PCNA). J Biol Chem. 277(47):45331-7.
Schmidt KH, Abbott C, and Leach DR, (2000) Two opposing effects of mismatch repair on CTG repeat instability in Escherichia coli. Mol Microbiol. 35(2):463-71.
Cancer Biology Ph.D. Program
H. Lee Moffitt Cancer Center, MRC-4 East
12902 Magnolia Drive
Tampa, Florida 33612
Phone: 813-745-6876
E-mail: CancerPHD@moffitt.org
Copyright © 2000 University of South Florida