Kristina H. Schmidt
Kristina H. Schmidt
Assistant Professor
Contact
Office: BSF 211
Phone: 813/974-1592
Email:
Education
M.Sc. Biology, University of Leipzig ( Germany ), 1995
Ph.D. Biology, University of Edinburgh ( UK ), 1999
Postdoctoral Fellow, Ludwig Institute for Cancer Research, University of California - San Diego
Research
Genome Instability, Spontaneous and Induced DNA Damage, DNA Replication, Recombination,
Repair, Cell Cycle Checkpoints, Cancer Genetics
Current Research:
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.
Of particular interest to me are 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. My current work 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.
Current Courses
Recent Publications
Vijayakumar S, Chapados BR, Schmidt KH, Kolodner RD, Tainer JA, Tomkinson AE. (2007) The C-terminal domain of yeast PCNA is required for physical and functional interactions with Cdc9 DNA ligase. Nucleic Acids Res. 35(5):1624-37.
Schmidt KH and Kolodner RD. (2006) Suppression of spontaneous genome rearrangements in yeast DNA helicase mutants. Proc Natl Acad Sci U S A.103(48):18196-201.
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 409:462-476.
Smolka MB, Albuquerque CP, Chen S, Schmidt KH, Wei XX, Kolodner RD, and Zhou H. (2005) Dynamic changes in protein-protein interaction and protein phosphorylation probed by amine reactive isotope tag. Mol Cell Proteomics 4(9):1358-69.
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.
Cromie GA, Millar CB, Schmidt KH, and Leach DR. (2000) Palindromes as substrates for multiple pathways of recombination in Escherichia coli. Genetics. 154(2):513-22.
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.