David Kirkpatrick, PhD
Yeast molecular genetics, Gene disruption, Mutational screening and analysis, Micro-array genome analysis
The Kirkpatrick lab is interested in understanding the mechanisms of DNA repair, and the cellular processes in which they are involved, in the yeasts Saccharomyces cerevisiae and Candida albicans.
Meiotic DNA Repair in S. cerevisiae: Recombination is an essential process during meiosis that generates diversity, ensures the proper segregation of chromosomes, and acts to repair DNA damage. Three repair pathways have been identified genetically for meiotic mismatch repair: the first pathway is responsible for base-base mismatches, while the second and third are required for repair of large loops. Mutant screens to identify novel genes that are involved in these repair pathways are being conducted. Three different screens are ongoing or in the process of being set up – a mitotic screen based on loop repair within the ADE2 gene, a screen based on loop repair during meiosis, and a collaboration to screen all of the deletions of the non-essential genes in the S. cerevisiae Yeast Deletion Strain Bank.
Another goal of the lab is identify the factors controlling the meiotic stability of a human minisatellite tract inserted into the yeast genome. This tract undergoes length alterations and rearrangements in a meiosis-specific manner. The mechanisms and gene products responsible for these processes are under investigation. Genes involved in meiotic recombination and DNA loop repair are required for tract stability. The structural factors of the minisatellite that influence stability include the total length of the tract, and the degree of sequence variation within the tract. Alterations in the minisatellite tract in humans have been correlated with various cancer susceptibilities; determination of the components responsible for these alterations will be important in understanding the etiology of these diseases.
DNA Repair Pathways in C. albicans: Candida albicans is a commensal organism in humans, but is also an opportunistic pathogen, especially in immunocompromised individuals. We are investigating the various DNA repair pathways (base excision repair, nucleotide excision repair, mismatch repair, and double-strand break repair) in Candida. The long-term goal of this project is to identify the cellular DNA repair factors that act on the genome of Candida, and the role that those factors play in the acquisition of antifungal drug resistance by the yeast, to aid in drug design and improve patient recovery percentages.
Legrand, M., Chan, C.L., Jauert, P.A., and D. T. Kirkpatrick (2008) Analysis of Base Excision and Nucleotide Excision Repair in Candida albicans. Microbiology 154: 2446-2456
Jensen, L.E., Jauert, P. A. and Kirkpatrick, D.T. (2005) The Large Loop Repair and Mismatch Repair Pathways Act on Distinct Substrates During Meiosis. Genetics 170: 1033-1043.
Jauert, P.A. and Kirkpatrick, D.T. (2005) Length and Sequence Heterozygosity Differentially Affect HRAS1 Minisatellite Stability During Meiosis In Yeast. Genetics 170: 601-612.
Borts, R. H. and Kirkpatrick, D.T. (2005) The Role of the Genome in Meiotic Recombination. Invited Book Chapter - “The Implicit Genome”, editor: Lynn Caporale.
Jauert, P. A., Jensen, L. E. and Kirkpatrick, D. T. (2005) A Novel Yeast Genomic DNA Library On a Geneticin-resistance Vector. YEAST 22: 653-657.
Sia, E. A. and Kirkpatrick, D. T. (2005) The Yeast MSH1 Gene Is Not Involved in DNA Repair or Recombination During Meiosis. DNA Repair, 4: 253-261.
Jauert, P. A., Edmiston, S. N., Conway, K., and D. T. Kirkpatrick. (2002) “RAD1 Controls the Meiotic Expansion of the Human HRAS1 Minisatellite in Saccharomyces cerevisiae”. Molecular and Cellular Biology 22: 953-964.
Kearney, H. M., Kirkpatrick, D. T., Gerton, J. L., and T. D. Petes. (2001) “Meiotic Recombination Involving Heterozygous Large Insertions in S. cerevisiae: Formation and Repair of Large, Unrepaired DNA Loops”. Genetics 158: 1457-1476.
Kirkpatrick, D. T., Ferguson, J. R., Petes, T. D., and L. S. Symington. (2000) “Decreased Meiotic Intergenic Recombination and Increased Meiosis I Nondisjunction in exo1 Mutants of Saccharomyces cerevisiae”. Genetics 156: 1549-1557.
Kirkpatrick, D. T. (1999) "Roles of the DNA Mismatch Repair and Nucleotide Excision Repair Proteins During Meiosis in the Yeast Saccharomyces cerevisiae" (invited review), Cellular and Molecular Life Sciences 55: 437-449.
Kirkpatrick, D. T., Fan, Q.-Q., and T. D. Petes. (1999) "Maximal Stimulation of Meiotic Recombination By a Yeast Transcription Factor Requires the Transcription Activation Domain and a DNA Binding Domain". Genetics 152: 101-115.
Kirkpatrick, D. T., Wang, Y.-H., Dominska, M., Griffith, J. D., and T. D. Petes. (1998) "Control of Meiotic Recombination and Gene Expression in Yeast by a Simple Repetitive DNA Sequence that Excludes Nucleosomes". Molecular and Cellular Biology 19: 7661-7671.
Kirkpatrick, D. T., Dominska, M., and T. D. Petes. (1998) "Conversion-type and restoration-type repair of DNA mismatches formed during meiotic recombination in Saccharomyces cerevisiae". Genetics 149: 1693-1705.
Kirkpatrick, D. T. and T. D. Petes. (1997) "Repair of DNA Loops Involves DNA Mismatch and Nucleotide Excision Repair Proteins" Nature 387: 929-931.
Kirkpatrick, D. T. (1997) "Deletion of Flanking ARS Elements Does Not Affect Meiotic Recombination at the HIS4 Locus in Yeast" Current Genetics 31: 106-111.
To view these and other publications visit http://www.ncbi.nlm.nih.gov/PubMed
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