The parent NIH grant has supported the development of methods for examining DNA-protein complexes by electron microscopy (EM), and transferring these methods to other laboratories. One research focus involves telomere structure. Here, a pressing need is to develop yeast systems which will allow EM to be used to probe telomere structure. Dr. Tomaska at Comenius University is highly experienced in yeast biochemistry and genetics. Two short collaborative visits he made to the US laboratory resulted in two papers demonstrating the feasibility and productivity of this international collaboration. Funding is now required to establish and foster further work. Dr. Tomaska will carry out the yeast developmental work in his laboratory and then obtain training in the EM preparative methods in the US laboratory with the goal of establishing these methods at Comenius University.
The first Aim i s the development of a S. cerevisiae minichromosome system for isolation and visualization of yeast telomeres. The minichromosome system developed by Runge and Zakian will be optimized for the isolation of multicopy linear minichromosomes on sucrose gradients with replication and telomere-specific proteins bound. Using EM and electrophoretic methods, the structure of the yeast telomeres will be examined with and without specific telomere-binding proteins.
The second aim i s to study the replication of yeast linear mitochrondrial genomes as a model system for elucidation of alternative, telomerase-independent, pathways of telomere maintenance. Proteins that specifically interact with the terminal structures of linear mtDNA molecules will be characterized further and examined by EM. The nature of the nuclear control over the replication of mitochondrial telomeres will be studied to analyze the specific coordination between the nuclear and mitochondrial genomes. This research will be primarily done in The Slovak Republic as an extension of NIH grant R01-GM31819-17.

Agency
National Institute of Health (NIH)
Institute
Fogarty International Center (FIC)
Type
Small Research Grants (R03)
Project #
5R03TW005654-03
Application #
6604295
Study Section
International and Cooperative Projects 1 Study Section (ICP)
Program Officer
Katz, Flora N
Project Start
2001-08-01
Project End
2006-06-30
Budget Start
2003-07-01
Budget End
2006-06-30
Support Year
3
Fiscal Year
2003
Total Cost
$40,320
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Valach, Matus; Pryszcz, Leszek P; Tomaska, Lubomir et al. (2012) Mitochondrial genome variability within the Candida parapsilosis species complex. Mitochondrion 12:514-9
Valach, Matus; Farkas, Zoltan; Fricova, Dominika et al. (2011) Evolution of linear chromosomes and multipartite genomes in yeast mitochondria. Nucleic Acids Res 39:4202-19
Gunisova, Stanislava; Bartosova, Zdenka; Kramara, Juraj et al. (2010) Formation of C-terminally truncated version of the Taz1 protein employs cleavage-box structure in mRNA. Biochem Biophys Res Commun 392:391-6
Kramara, Juraj; Willcox, Smaranda; Gunisova, Stanislava et al. (2010) Tay1 protein, a novel telomere binding factor from Yarrowia lipolytica. J Biol Chem 285:38078-92
Kinsky, Slavomir; Mihalikova, Andrea; Kramara, Juraj et al. (2010) Lack of the catalytic subunit of telomerase leads to growth defects accompanied by structural changes at the chromosomal ends in Yarrowia lipolytica. Curr Genet 56:413-25
Fricova, Dominika; Valach, Matus; Farkas, Zoltan et al. (2010) The mitochondrial genome of the pathogenic yeast Candida subhashii: GC-rich linear DNA with a protein covalently attached to the 5' termini. Microbiology 156:2153-63
Nosek, Jozef; Holesova, Zuzana; Kosa, Peter et al. (2009) Biology and genetics of the pathogenic yeast Candida parapsilosis. Curr Genet 55:497-509
Tomaska, Lubomir; Nosek, Jozef; Kramara, Juraj et al. (2009) Telomeric circles: universal players in telomere maintenance? Nat Struct Mol Biol 16:1010-5
Tomaska, Lubomir; Nosek, Jozef (2009) Telomere heterogeneity: taking advantage of stochastic events. FEBS Lett 583:1067-71
Visacka, Katarina; Gerhold, Joachim M; Petrovicova, Jana et al. (2009) Novel subfamily of mitochondrial HMG box-containing proteins: functional analysis of Gcf1p from Candida albicans. Microbiology 155:1226-40

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