The potential functional significance of chromatin structural features associated with the (putative) control regions of three yeast genes, galactokinase, histone H2B and 35S rDNA will be evaluated, in order to determine whether there is a causative relationship between these structural features and the (unknown) features involved in transcriptional aspects of the control of gene expression in eukaryotic organisms. In parallel, work will be directed towards elucidating the physical forces involed in stabilizing anomalous control chromatin features and towards determining if there are any anomalous DNA conformational flexibility features associated with control sequence DNA. In vitro mutagenesis studies will be used to assess the dependence of control chromatin features and control sequence DNA conformational flexibility on DNA sequence. Various assays of gene expression level (viability, mRNA production, normal regulation) will be correlated with the physical data. A new technique for precise assessment of in nucleo DNA-protein interactions will be developed, to increase the sensitivity level for detecting anomalous chromatin structural features. A hybrid gene system will be used to try to develop a technique to obtain functional and structural data on one of the genes in a highly repeated gene set (35S rDNA). The goal of all these experiments is to gain some understanding of how eukaryotic cells control gene expression. An understanding of the bases for the control of gene expression is absolutely essential in understanding and solving a number of outstanding health problems, for example, cancer, aging and processes like abnormal development, which affect humans and other multicellular organisms. However, the latter systems are very complex. If one can gain an understanding of some of the bases for control of gene expression in a system like yeast, which has fewer complexities and is amenable to very favorable manipulations, this knowledge will be useful in helping to suggest approaches which can lead to understanding in the more complex systems.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Modified Research Career Development Award (K04)
Project #
5K04CA000911-02
Application #
3071507
Study Section
Genetics Study Section (GEN)
Project Start
1984-08-01
Project End
1989-07-31
Budget Start
1985-08-01
Budget End
1986-07-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Arizona State University-Tempe Campus
Department
Type
Schools of Arts and Sciences
DUNS #
188435911
City
Tempe
State
AZ
Country
United States
Zip Code
85287
McNamara, James O; Kolonias, Despina; Pastor, Fernando et al. (2008) Multivalent 4-1BB binding aptamers costimulate CD8+ T cells and inhibit tumor growth in mice. J Clin Invest 118:376-86
McNamara 2nd, James O; Andrechek, Eran R; Wang, Yong et al. (2006) Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras. Nat Biotechnol 24:1005-15
Lohr, D; Lopez, J (1995) GAL4/GAL80-dependent nucleosome disruption/deposition on the upstream regions of the yeast GAL1-10 and GAL80 genes. J Biol Chem 270:27671-8
Mullins, T D; Kern, H F; Metzgar, R S (1991) Ultrastructural differentiation of sodium butyrate-treated human pancreatic adenocarcinoma cell lines. Pancreas 6:578-87
Rainbow, M; Lopez, J; Lohr, D (1989) The yeast GAL1-10 UAS region readily accepts nucleosomes in vitro. Biochemistry 28:7486-90
Nelson, R W; Rainbow, M J; Lohr, D E et al. (1989) Volatilization of high molecular weight DNA by pulsed laser ablation of frozen aqueous solutions. Science 246:1585-7
Kreuzer, K N; Yap, W Y; Menkens, A E et al. (1988) Recombination-dependent replication of plasmids during bacteriophage T4 infection. J Biol Chem 263:11366-73
Kreuzer, K N; Engman, H W; Yap, W Y (1988) Tertiary initiation of replication in bacteriophage T4. Deletion of the overlapping uvsY promoter/replication origin from the phage genome. J Biol Chem 263:11348-57
Lohr, D; Torchia, T (1988) Structure of the chromosomal copy of yeast ARS1. Biochemistry 27:3961-5
Murphy, S P; Garbern, J; Odenwald, W F et al. (1988) Differential expression of the homeobox gene Hox-1.3 in F9 embryonal carcinoma cells. Proc Natl Acad Sci U S A 85:5587-91

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