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 Dr. Heather E. Lorimer
Associate Professor
Molecular Biology and Microbiology
330-941-7179
helorimer AT ysu DOT edu
WBSH 3052
Website: http://www.cc.ysu.edu/~helorime/
A.B. University of Chicago, Biology
M.A. Columbia University, Biological Sciences, Molecular Biology
M.Ph. Columbia University, Biological Sciences, Molecular Biology
Ph.D. Columbia University, Biological Sciences, Molecular Biology
Research Interests
My laboratory's primary work involves the mechanisms of replication of mitochondrial DNA.
Mitochondria are small organelles that function as the biological powerhouses of the cell. Mitochondria contain their own genome (mtDNA), which replicates independently of the cycles that control chromosomal DNA replication in the nucleus. Defects in mitochondrial DNA are being increasingly implicated in a variety of degenerative human diseases.
Little is currently known about the relative transmission of normal and mutant mtDNAs, or about the control of mtDNA replication in general. The yeast Saccharomyces cerevisiae presents a system where competitive transmission of wild-type and mutant mtDNAs is quite accessible to analysis. Some mutant yeast mtDNAs are preferentially inherited. Some of these mtDNAs also appear to have a replication advantage that contributes to disease processes. We use a 2-dimensional gel electrophoretic procedure to analyze the structures of replicating DNA to help elucidate the mechanism of replication and inheritance. In collaboration with Dr. Ian Holt at MRC Dunn Human Nutrition Unit in Cambridge, England we have examined the general structure and replicating of human mitochondrial DNA and the fission yeast Schizosaccharomyces pombe.
Several nuclear genes that have been hypothesized to be involved in mtDNA replication are also under current investigation in our laboratory. RPO41 encodes the yeast mitochondrial RNA polymerase catalytic subunit, MGT1/CCE1 encodes a recombination junction resolvase, and MHR1 encodes a protein involved in homologous recombination. Earlier hypotheses predicted that the RNA polymerase would be essential for mtDNA replication. It is not, though it may influence it. On the other hand eliminating the homologous recombination and resolving genes does eliminate mtDNA. We are actively pursuing the interactions of these gene products with the process of mtDNA replication. Ultimately this work may lead to more basic understanding of the process of mtDNA replication and how it is regulated.
Additional collaborations include Chloroplast DNA sequences diversity in old growth forest trees in Zoar valley, NY, as well as DNA structure analysis in cancer cells and gene manipulation other fungal, bacterial and viral systems.
Selected Publications
Arnett, D.R., H.E. Lorimer, and D.K. Asch. 2009. Catabolite repression directly affects transcription of the qa-y gene of Neurospora crassa. Fungal Genetics and Biology (in press) Available online 21 February 2009.
Gilloteaux J, Jamison JM, Lorimer HE, Jarjoura D, Taper HS, Calderon PB, Neal DR, Summers JL. J. 2004. Autoschizis: a new form of cell death for human ovarian carcinoma cells following ascorbate: menadione treatment. Nuclear and DNA degradation. Tissue Cell, 36: 197-209.
von Gruenigen, Vivian E.; Jamison, James M.; Gilloteaux, Jacques; Lorimer, Heather E.; Summers, Marcia; Pollard, Robert R.; Gwin, Carley A.; Summers, Jack L. 2003. The in vitro antitumor activity of vitamins C and K3 against ovarian carcinoma. Anticancer Res. 23(4) 3279-3288.
Heather E. Lorimer Analysis of Native Forms of Mitochondrial DNA by 2D Gel Electrophoresis. in "Methods in Molecular Biology: Mitochondrial DNA: Methods and Protocols." 2002 The Humana Press Inc., Totowa, N.J.
Holt, I.J., H. E. Lorimer, and H.T. Jacobs. 2000. Coupling leading- and lagging- strand synthesis of mammalian mitochondrial DNA. Cell 100: 515-524.
Lorimer, H. E., B. Brewer, and W. L. Fangman. 1995. A test of the transcription model for the biased inheritance of yeast mitochondrial DNA. Mol. Cell. Biol. 15 (9):4803-4809.
Lockshon, D., S. G. Zweifel, L. L. Freeman, H. E. Lorimer, B. J. Brewer, and W. L. Fangman. 1995. A role for recombination junctions in the segregation of mitochondrial DNA in yeast. Cell 81:947-955.
Reynisdottir*, I., H. E. Lorimer*, P. N. Friedman, E. H. Wang, and C. Prives. Phosphorylation and active ATP hydrolysis are not required for SV40 T antigen hexamer formation. 1993. J. Biol. Chem. 268(33):24647-24654. (*The first two authors contributed equally to this report)
Lorimer, H. E., I. Reynisdottir, S. Ness, and C. Prives. 1993. Unusual Properties of a replication-defective mutant SV40 large T antigen. Virology 192:402-414.
Lorimer, H.E., Wang, E.H., Prives, C. 1991. The DNA-binding properties of Polyomavirus Large-T Antigen are altered by ATP and other nucleotides. Journal of Virology 65: (2) 687-699 Feb. 1991 |
