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Biochemistry, Biophysics, and Structural Biology Commons™
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- RNA (3)
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Articles 1 - 15 of 15
Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
A Study Of The Effects Of Inosine Incorporation Into Dna Due To Defects In Purine Biosynthesis In Escherichia Coli, Jonathan Spence Church
A Study Of The Effects Of Inosine Incorporation Into Dna Due To Defects In Purine Biosynthesis In Escherichia Coli, Jonathan Spence Church
Legacy Theses & Dissertations (2009 - 2024)
Deamination of purine bases can result in the formation of xanthine and hypoxanthine which can be miscoding and mutagenic in DNA. There are several mechanisms for the introduction of deaminated bases into DNA including simple hydrolysis, nitrosative chemistry and through the action of deaminase enzymes. A fourth method was recently presented which describes how deaminated purines can be incorporated into DNA due to defects in purine biosynthesis. Using fluctuation analysis, spontaneous mutation rates were studied in bacterial mutants that were deficient in specific genes involved in purine biosynthesis and dNTP precursor pool maintenance, including purA (adenylosuccinate synthetase), guaA (GMP synthetase), …
Dna Repair Fidelity And Cancer : Structural And Kinetic Insights From Dna Polymerase Beta Mutator Variants, Chelsea Lynne Gridley
Dna Repair Fidelity And Cancer : Structural And Kinetic Insights From Dna Polymerase Beta Mutator Variants, Chelsea Lynne Gridley
Legacy Theses & Dissertations (2009 - 2024)
DNA polymerases are essential for genome replication and DNA repair in all living organisms. Precise DNA replication is critical for the preservation of genomic stability. Any insult, endogenous/exogenous, to cellular DNA requires properly functioning repair polymerases. In eukaryotes, DNA polymerase beta, a small enzyme (39 kDa), plays an important role in DNA repair during the base excision repair pathway. Pol beta catalyzes the incorporation of nucleotides in small stretches (1-6 nucleotides) of damaged double-stranded DNA. Should gap-filling synthesis by pol beta be compromised, mutations in genomic DNA accumulate, which are frequently linked to human diseases, including cancers. For this reason, …
Sirtuin 6 : A Review Of Biological Affects And Potential Therapeutic Properties, Jade Beauharnois
Sirtuin 6 : A Review Of Biological Affects And Potential Therapeutic Properties, Jade Beauharnois
Legacy Theses & Dissertations (2009 - 2024)
ABSTRACT: Sirtuins, possessing either histone deacetylase or mono-ribosyltransferase activity, regulate important biological pathways in bacteria, archaea and eukaryotes. The term Sir2 comes from the yeast 'silent mating-type information regulation 2' gene, a gene directing cellular regulation in yeast. Sirtuins have been implicated in aging, regulation of transcription, apoptosis and stress resistance, in addition to energy efficiency and metabolism. In mammals, a variety of sirtuin family members are genetically encoded to include sirtuins 1-7 (SIRT1-SIRT7). SIRT6 is a human sirtuin of interest in a variety of research areas, influencing the genomic instability, metabolic defects and degenerative pathologies associated with aging. Until …
Ultraviolet Resonance Raman Spectroscopy For Characterization Of Rna Structure And Thermodynamics, Joseph Dustin Handen
Ultraviolet Resonance Raman Spectroscopy For Characterization Of Rna Structure And Thermodynamics, Joseph Dustin Handen
Legacy Theses & Dissertations (2009 - 2024)
Raman spectroscopy is a technique well suited for the study of biological molecules such as proteins, peptides, or RNAs. By utilizing an ultraviolet resonance Raman (UVRR) instrument, we are afforded a tremendous increase in sensitivity because of resonance enhancement. Additionally, this technique does not require any labeling. Moreover, this technique is better suited for studying biological systems than infrared absorption due to reduced interference from water. In this study, we apply techniques we have developed for the study of protein and peptide fibrillation to a model RNA homodimer. We demonstrate that UVRR spectroscopy is uniquely suited to monitoring the free …
Inhibition Of Glutamate Receptors By Constructing Bipartite Rna Aptamers, Jeffrey Hebert
Inhibition Of Glutamate Receptors By Constructing Bipartite Rna Aptamers, Jeffrey Hebert
Legacy Theses & Dissertations (2009 - 2024)
The relationship of excessive activity of AMPA-type glutamate receptors, and cell death, has long provided researchers a means of investigating neurodegenerative disorders, such as Parkinson's Disease (PD) and amyotrophic lateral sclerosis (ALS). Inhibitors of AMPA receptor channels, including chemical and nucleic acid molecules such as RNA aptamers, have served as potential therapeutic agents and treatment of neurodegenerative disorders. In this study, building bipartite aptamers to enhance inhibitory potency, as compared with a monomeric aptamer of AMPA receptor, is described. An enhanced potency is due, at least in part; to the proximity effect in bipartite structures or binding of a monomeric …
Characterization Of The Calmodulin-Ryanodine Receptor Interaction By Cryo-Electron Microscopy, Xiaojun Huang
Characterization Of The Calmodulin-Ryanodine Receptor Interaction By Cryo-Electron Microscopy, Xiaojun Huang
Legacy Theses & Dissertations (2009 - 2024)
Ryanodine receptor (RyR) is a key player in excitation-contraction coupling (E-C coupling). Calmodulin (CaM) is one of the important regulatory factors of RyR. Two mammalian RyR isoforms, RyR1 and RyR2, are highly enriched in skeletal and cardiac muscle, respectively. Apo-calmodulin weakly activates RyR1 but inhibits RyR2, whereas Ca2+-calmodulin inhibits both the isoforms. Previous cryo-electron microscopy studies showed distinctly different binding locations on RyR1 for the two states of calmodulin. However, recent studies employing fluorescence resonance energy transfer appeared to challenge these findings. In chapter 1, using cryo-electron microscopy, we have determined that a mutant calmodulin, which is incapable of binding …
Interactions Of The Human Immunodeficiency Virus Type 1 Nucleocapsid Protein With Non-Hiv-Derived Nucleic Acids : Implications For The Viral Replication Cycle, Abhijit Padmakar Jadhav
Interactions Of The Human Immunodeficiency Virus Type 1 Nucleocapsid Protein With Non-Hiv-Derived Nucleic Acids : Implications For The Viral Replication Cycle, Abhijit Padmakar Jadhav
Legacy Theses & Dissertations (2009 - 2024)
During attempts to develop aptamers that bind to the nucleocapsid protein of HIV-1 (i.e. NCp7) with high affinity, a heretofore unreported property of the protein--the ability to mediate degradation of nucleic acids, was discovered. Using λ DNA as a model nucleic acid system, it was shown that NCp7-mediated degradation of nucleic acids is non-specific, depends on incubation time, the concentration of NCp7, and the presence of divalent and monovalent cations. It was further demonstrated that degradation can be abrogated if NCp7 is pre-incubated with NCp7-inhibitors. Lyophilization of NCp7 can induce irreversible changes in its secondary structure that result in loss …
Amyloid Fibril Polymorphism : Structure, Supramolecular Chiraliy And Spontaneous Interconversion, Dzmitry Kurouski
Amyloid Fibril Polymorphism : Structure, Supramolecular Chiraliy And Spontaneous Interconversion, Dzmitry Kurouski
Legacy Theses & Dissertations (2009 - 2024)
Specific protein aggregation has been linked to more than 25 severe human maladies including prion, Alzheimer's, and Parkinson's diseases. These important malfunctions are often referred to as 'conformational' disorders and result from the conversion of a normal isoform of a protein into a specific b-sheet rich polymeric amyloid form. This work elaborates a comprehensive characterization of amyloids and dedicated to the investigation of the fibril polymorphism using advanced microscopic tools, such as Atomic Force and Scanning Electron microcopies, together with several vibrational spectroscopy techniques, such as Raman, Infrared and Vibrational Circular Dichroism. A new type of protein folding-aggregation phenomenon, spontaneous …
The Role Of Chromatin And Cofactors In The Transcriptional Memory Effect Exerted In Saccharomyces Cerevisiae, Emily Leigh Paul
The Role Of Chromatin And Cofactors In The Transcriptional Memory Effect Exerted In Saccharomyces Cerevisiae, Emily Leigh Paul
Legacy Theses & Dissertations (2009 - 2024)
Abf1 and Rap1 are functionally similar general regulatory factors (GRFs) found in Saccharomyces cerevisiae . Abf1, in its role as a transcriptional activator, exerts a memory effect on some genes under its control. This effect results in transcription levels remaining steady when Abf1 dissociates from its binding site in a conditional mutant. In contrast, Rap1 fails to elicit the same effect on its regulatory targets. Transcriptional memory effects have been observed in many fields of study, including immunology, cancer, and stem cells, and conservation of transcription machinery will allow studies in yeast to be applied to higher organisms.
Structural And Functional Characterization Of Dna Polymerase Ss Mutator Mutants, Sneha Rangarajan
Structural And Functional Characterization Of Dna Polymerase Ss Mutator Mutants, Sneha Rangarajan
Legacy Theses & Dissertations (2009 - 2024)
DNA Polymerase ß (polß) plays a crucial role in repairing damaged DNA in a process called Base Excision Repair (BER). BER is a major pathway of DNA repair, making this system absolutely vital for maintaining genomic integrity. Recent studies estimate 30% of human tumors to contain polß variants that led us to believe that there is a high degree of association between mutations in polß and cancer. In this pathway, after recognition and excision of the damaged base, the DNA is cleaved at an apurinic (AP) site by AP endonuclease leaving behind a 3' hydroxyl and 5' deoxyribose phosphate (dRP). …
Gld-1 Represses Its Puf Mrna Targets Prior To/At Initiation Of Translation In The C.Elegans Germline, Gautham Sarathy
Gld-1 Represses Its Puf Mrna Targets Prior To/At Initiation Of Translation In The C.Elegans Germline, Gautham Sarathy
Legacy Theses & Dissertations (2009 - 2024)
The C.elegans germline offers an ideal system to study posttranscriptional regulation of gene expression as it is a major mechanism through which the control over gene expression is achieved. GLD-1 (defective in GermLine Development) is a maxi-KH motif containing RNA binding protein that controls various aspects of germline development from decision over germcell proliferation vs. meiotic entry to the production of mature gametes suggesting that GLD-1 likely controls many mRNA targets.
The Role Of Ess1 In Survival, Morphogenetic Switching And Transcription In The Fungal Pathogen Candida Albicans, Dhanushki Poornima Samaranayake
The Role Of Ess1 In Survival, Morphogenetic Switching And Transcription In The Fungal Pathogen Candida Albicans, Dhanushki Poornima Samaranayake
Legacy Theses & Dissertations (2009 - 2024)
Candida albicans is a fungal pathogen that causes serious infections among immune-compromised patients and premature infants. C. albicans can become drug resistant, therefore, identifying new antifungal drug targets is an important goal. Here, we study a peptidyl-prolyl cis/trans isomerase called Ess1 as a potential drug target. Ess1 is conserved among pathogenic fungi, and therefore, potential inhibitors of Ess1 should display a broad spectrum of activity. We confirm that Ess1 is essential for growth in Candida albicans, but unlike the previously published find, deleting one copy of the C. albicans ESS1 gene did not affect morphogenetic switching. However, further reducing activity …
Selection Of Chemically Modified Rna Aptamers Against The Glua2q Flop Ampa Receptor, Hyojung Seo
Selection Of Chemically Modified Rna Aptamers Against The Glua2q Flop Ampa Receptor, Hyojung Seo
Legacy Theses & Dissertations (2009 - 2024)
The á-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors play an important role in neurotransmission and synaptic plasticity in the central nervous system. Excessive activity of these receptors has been implicated in some neurodegenerative diseases, such as Parkinson's disease, ischemic stroke and amyotrophic lateral sclerosis (ALS). AMPA receptor inhibitors are therefore drug candidates for potential treatment of these neurological disorders and diseases. The objective of my MS thesis work is to develop a stable aptamer so that it can be tested and used in vivo where the aptamer must be exposed to ribonucleases. To do this, I prepared a library containing RNAs with 2'-Fluoro …
Structure And Function Of Non-Coding Regulatory Rna Domains, Nakesha L. Smith
Structure And Function Of Non-Coding Regulatory Rna Domains, Nakesha L. Smith
Legacy Theses & Dissertations (2009 - 2024)
Ribonucleic acid (RNA) has been found to be a very versatile molecule, exhibiting countless functions and can act as a catalyst in biochemical reactions. These functions have typically been attributed to the unique structures that it forms. Novel non-coding RNAs capable of regulating gene expression are still being discovered, and the scope of the RNA world is still being uncovered. The structure function relationship of two different types of non-coding RNA has been investigated: riboswitches and sxRNAs. UV-monitored thermal denaturation experiments, Nuclear Magnetic Resonance spectroscopy, native gel electrophoresis and an in vivo luciferase assay were used to investigate the structural …
Mechanism Of Inhibition Of The Glua2 Receptors By N-3 Derivatives Of 2,3-Benzodiazepines With C-4 Methyl Group, Congzhou Wang
Mechanism Of Inhibition Of The Glua2 Receptors By N-3 Derivatives Of 2,3-Benzodiazepines With C-4 Methyl Group, Congzhou Wang
Legacy Theses & Dissertations (2009 - 2024)
α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are one of the three subtypes of ionotropic glutamate receptors. AMPA receptors mediate fast synaptic neurotransmission in the central nervous system (CNS). Over-activation of calcium permeable AMPA receptors causes intracellular calcium overload, which leads to neurodegeneration and cell death. As such, AMPA receptors have been implicated in a number of neurological disorders and diseases, such as epilepsy, amyotrophic lateral sclerosis (ALS), and Parkinson's disease. 2,3-Benzodiazepine derivatives (or GYKI compounds) are a group of structurally similar compounds synthesized as inhibitors of AMPA receptors, and they have been used as potential drug candidates for the treatment of various …