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Theses and Dissertations in Biomedical Sciences

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Translational Regulation Of The C-Jun Proto-Oncogene, Anil Sehgal Apr 1994

Translational Regulation Of The C-Jun Proto-Oncogene, Anil Sehgal

Theses and Dissertations in Biomedical Sciences

The v-jun oncogene was originally isolated from the ASV17 virus in 1987. Ever since its isolation, extensive work has been done to understand the role of the v-jun oncogene in cell transformation. The c-Jun protein is a transcription factor which binds to the DNA target TGACTCA. The c-Jun protein binds to DNA in the form of dimers. It can form homodimers with itself and heterodimers with Jun family (JunB and JunD), Fos family (FosB, Fra1 and Fra2), or with CREB family members through the leucine zipper motif. Because the c-jun proto-oncogene plays an important role in cell transformation, extensive work …


Subunit Interactions Of Recombinant Hiv-1 Reverse Transcriptase With Mutations At L289, Jacquelyn R. Smith Jan 1994

Subunit Interactions Of Recombinant Hiv-1 Reverse Transcriptase With Mutations At L289, Jacquelyn R. Smith

Theses and Dissertations in Biomedical Sciences

Reverse transcriptase (RT) is a dimeric enzyme required for replication of the human immunodeficiency virus (HIV). If the subunits of the RT dimer are dissociated, the enzyme is no longer active; therefore, identification of subunit binding sites could lead to potential targets for antiviral therapy. In order to identify where subunit binding of RT occurs, mutations were made at leucine (L) 289, a residue believed to be involved in dimerization through hydrophobic interactions with other leucines. L289 is the central leucine of a leucine repeat sequence which resembles a leucine zipper protein-DNA binding motif. Two mutations, leucine to arginine (L289R) …


An Analysis Of Mitochondrial Dna In Rett Syndrome And Other Neurodegenerative Disorders, Catherine Erickson Burgess Jan 1994

An Analysis Of Mitochondrial Dna In Rett Syndrome And Other Neurodegenerative Disorders, Catherine Erickson Burgess

Theses and Dissertations in Biomedical Sciences

Mitochondrial dysfunction resulting from mutations on mitochondrial DNA (mtDNA) is being recognized in a growing spectrum of diseases. These diseases, resulting from single base mutations, large deletions, or insertions, have been largely neuromuscular in origin. However, as an understanding of the effects of mtDNA mutations progresses, attention is now focusing on neurodegenerative diseases. Rett Syndrome (RS), a progressive neurodegenerative disease with predominantly female cases, demonstrates morphologic mitochondrial changes, mitochondrial enzyme deficiencies and maternal inheritance (characteristic of mtDNA diseases). No investigation of mtDNA involvement has been previously conducted and, to date, no biological marker exists for this disorder.

Our preliminary studies …


Studies On Type I And Type Ii Dna Topoisomerases From Mammalian Mitochondria, Jia-Hwei Lin Jul 1993

Studies On Type I And Type Ii Dna Topoisomerases From Mammalian Mitochondria, Jia-Hwei Lin

Theses and Dissertations in Biomedical Sciences

Mammalian mitochondria contain a unique DNA topoisomerase I with characteristics of both nuclear and bacterial type I DNA topoisomerases. This enzyme, purified from bovine liver, requires cations as cofactors and possesses optimal activity at pH 7.0, 37°C and either 150 mM K+ or Na+ ions. Similar to nuclear enzymes and different from the bacterial enzyme, divalent ions such as Ca2+ or Mg2+ will stimulate but are not essential for the enzymatic activity.

Like the nuclear DNA topoisomerase I, the mitochondrial enzyme is capable of relaxing both negatively and positively supercoiled DNA. The relaxation of negatively supercoiled DNA is …


Cloning A Putative Dna-Binding Protein Controlling The 5'Ltr Of The Copia Element In Drosophila, Horng-Yuan Kan Mar 1993

Cloning A Putative Dna-Binding Protein Controlling The 5'Ltr Of The Copia Element In Drosophila, Horng-Yuan Kan

Theses and Dissertations in Biomedical Sciences

Copia, a Drosophila retrotransposon, is constitutively expressed in all developmental stages, except the embryo in Drosophila melanogaster. The effect of random integration of the copia element results in phenotypic change in Drosophila. The regulatory sequences, controlling copia expression, are located within the 5'LTR. The DNA sequence in the 5'LTR and in the location between downstream of entire the 5' LTR and the initial translation site have been identified by mobilityshift binding assays and DNase I footprinting assays. The data reveals three protected regions: a TATA-binding site, the AT-1, and AT-2 binding sites. The TATA-binding site and AT-1 site are …


The Role Of Queuine Deficient Trna In Translational Control, Kathryn Lenore Hart Apr 1991

The Role Of Queuine Deficient Trna In Translational Control, Kathryn Lenore Hart

Theses and Dissertations in Biomedical Sciences

The purpose of this research was to study the effect of the level of tRNA modification with respect to queuine on translational efficiency. Transfer RNA from neoplastic cells is generally deficient with regard to certain hypermodified nucleosides found in normal cells. The hypothesis that was examined is whether or not the altered efficiency of translation can be correlated to the presence of queuine hypomodified tRNA. The loss of queuine in the anticodon may change the interaction of the tRNA's anticodon with its codon. Therefore, the translational complex may stall looking for a rare tRNA, or the stability of the complex …


The Role Of The Voltage Gradient In The Agarose Gel Electrophoresis Of Dna, David Wheeler Apr 1990

The Role Of The Voltage Gradient In The Agarose Gel Electrophoresis Of Dna, David Wheeler

Theses and Dissertations in Biomedical Sciences

In Part I of this dissertation, empirical equations for predicting DNA mobility during agarose gel electrophoresis (AGE) from voltage gradient are developed from the data of McDonnel (36) for electrophoresis in a 1.6% agarose gel. These equations represented the data well for DNA between 2 and 10 kilobase pairs (KBp) in length. A computer program, called GELSIM, which incorporates these equations is described in Part II. GELSIM was designed to allow researchers to analyze electrophoresis data by predicting the effect on DNA migration of altering the voltage of electrophoresis. In this way, electrophoretic banding patterns produced using different voltages could …


Molecular Study Of The B19 (Human) Pathogenic Parvovirus, Jamshed Ayub Jul 1988

Molecular Study Of The B19 (Human) Pathogenic Parvovirus, Jamshed Ayub

Theses and Dissertations in Biomedical Sciences

The B19 (human) parvovirus is a small single stranded DNA virus of 5.4 kilobases. B19 is specific for erythroid progenitor cells and has been propagated in vitro only with human erythroid bone marrow. Replication of viral DNA and the viral protein products of B19 appear similar to those of other animal parvoviruses. However, B19 differs from other parvoviruses in some important aspects, which include the initiation of all transcripts at a strong left side promoter (p6) and the absence of a functional internal promoter. B19 has an unusual transcription map which is described in this study.

The transcription map of …