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Full-Text Articles in Molecular Biology

A Study Of The Effects Of Inosine Incorporation Into Dna Due To Defects In Purine Biosynthesis In Escherichia Coli, Jonathan Spence Church Jan 2012

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 Jan 2012

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, …


Inhibition Of Glutamate Receptors By Constructing Bipartite Rna Aptamers, Jeffrey Hebert Jan 2012

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 Jan 2012

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 …


The Role Of Chromatin And Cofactors In The Transcriptional Memory Effect Exerted In Saccharomyces Cerevisiae, Emily Leigh Paul Jan 2012

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.


Gld-1 Represses Its Puf Mrna Targets Prior To/At Initiation Of Translation In The C.Elegans Germline, Gautham Sarathy Jan 2012

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 Jan 2012

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 …