Genetics Commons^™

Dna Polymerase Zeta-Dependent Mutagenesis: Molecular Specificity, Extent Of Error-Prone Synthesis, And The Role Of Dntp Pools, Olga V. Kochenova

Theses & Dissertations

Despite multiple DNA repair pathways, DNA lesions can escape repair and compromise normal chromosomal replication, leading to genome instability. Cells utilize specialized low-fidelity Translesion Synthesis (TLS) DNA polymerases to bypass lesions and rescue arrested replication forks. TLS is a highly conserved two-step process that involves insertion of a nucleotide opposite a lesion and extension of the resulting aberrant primer terminus. The first step can be performed by both replicative and TLS DNA polymerases and, because of non-instructive DNA lesions, often results in a nucleotide misincorporation. The second step is almost exclusively catalyzed by DNA polymerase ζ …

A Bioinformatics Methodology For The Annotation And Analysis Of Sperm Chromatin Remodeling Proteins In Sequenced Drosophila Species, Zain A. Alvi

Seton Hall University Dissertations and Theses (ETDs)

Spermatogenesis is the process by which mature functional spermatozoa are formed, and is initiated in the stem cell niche of the testes. During the post-meiotic stage of spermatogenesis, spermiogenesis, transition proteins facilitate the transformation of chromatin from a histone-based nucleosome structure to a protamine-based nucleosome structure. This study is aimed at analyzing genomic, transcript, and protein sequences of transition proteins in 13 sequenced Drosophila species. The Drosophila melanogaster spermatid specific transition protein-like protein (Tpl^94D) was used as the reference sequence in this study. An extensive bioinformatics approach was employed in establishing the Tpl^94D orthologs. We identified …

Study Of The Structure-Related Functions Of Eukaryotic Primase-Pol Alpha Complex During Replication, Yinbo Zhang

Theses & Dissertations

During eukaryotic replication primase•polymerase α (prim•polα) complex synthesizes de novo chimeric primers composed of about 10 nt RNA and 20 nt DNA, which are subsequently extended by main replicative DNA polymerases (pol), polε and polδ, on leading and lagging strands, respectively. It is estimated that prim•polα initiates more than 10 millions of lagging strand Okazaki fragments in human genome in each replication cycle. A concerted action of the two active sites, RNA pol and DNA pol, is required to ensure the efficient priming. A remarkable feature of the prim•polα complex is the “programmed” synthesis of the chimeric primer, where the …

Tackling Adverse Environment—Molecular Mechanism Of Plant Stress Response And Biotechnology Tool Development, Ning Yuan

All Dissertations

Abiotic and biotic stresses such as drought, salt, nutrition starvation, and pathogen infection are major factors threatening our agricultural production. With the rapidly increasing population and limited arable land area, genetic engineering of crops for new products with more stable and higher yield than conventional cultivars under adverse environment provides a powerful new tool for use in developing novel GMOs (Genetically Modified Organisms) to feed the large population in the immediate future. To develop novel GMOs with enhanced performance under adverse conditions, we need first to understand molecular mechanisms underlying plant stress response. To better understand how signaling transduction pathway …

Vascular Endothelial Growth Factor-A Gene Electrotransfer Promotes Angiogenesis In A Porcine Model Of Cardiac Ischemia, Anna A. Bulysheva, Barbara Hargrave, Nina Burcus, Cathryn G. Lundberg, Len Murray, Richard Heller

Bioelectrics Publications

This study aimed to assess safety and therapeutic potential of gene electrotransfer (GET) as a method for delivery of plasmid encoding vascular endothelial growth factor A (VEGF-A) to ischemic myocardium in a porcine model. Myocardial ischemia was induced by surgically occluding the left anterior descending coronary artery in swine. GET following plasmid encoding VEGF-A injection was performed at four sites in the ischemic region. Control groups either received injections of the plasmid without electrotransfer or injections of the saline vehicle. Animals were monitored for 7 weeks and the hearts were evaluated for angiogenesis, myocardial infarct size and left ventricular contractility. …

Heterologous Expression Of A Rice Mir395 Gene In Nicotiana Tabacum Impairs Sulfate Homeostasis, Ning Yuan, Shuangrong Yuan, Zhigang Li, Dayong Li, Qian Hu, Hong Luo

Publications

Sulfur participates in many important mechanisms and pathways of plant development. The most common source of sulfur in soil –SO₄²⁻– is absorbed into root tissue and distributed into aerial part through vasculature system, where it is reduced into sulfite and finally sulfide within the subcellular organs such as chloroplasts and mitochondria and used for cysteine and methionine biosynthesis. MicroRNAs are involved in many regulation pathways by repressing the expression of their target genes. MiR395 family in Arabidopsis thaliana has been reported to be an important regulator involved in sulfate transport and assimilation, and a high-affinity sulphate transporter …

The Role Of Daf-19 In Non-Ciliated Neurons: How Is Neural Development Regulated By Different Daf-19 Isoforms?, Zabdiel Ek Vazquez

Lawrence University Honors Projects

A degenerative disease-like phenotype, specifically reduction in synaptic protein levels in adult worms, is correlated with loss-of-function of the only RFX transcription factor gene, daf-19, in C. elegans. This gene encodes four known transcription factor isoforms, two of which are correlated with particular functions. The DAF-19C isoform activates genes responsible for cilia development, while DAF-19M is needed for cilia specification in males. A comparison of the transcriptome of daf-19 null and isogenic wild type adult worms suggests both positive and negative regulation of gene expression is correlated with the presence of DAF-19 proteins. We have assessed DAF-19 regulation …

Hiv Vaccines: Progress, Limitations And A Crispr/Cas9 Vaccine, Omar A. Garcia Martinez

Biology: Student Scholarship & Creative Works

ABSTRACT: The HIV-1 pandemic continues to thrive due to ineffective HIV-1 vaccines. Historically, the world’s most infectious diseases, such as polio and smallpox, have been eradicated or have come close to eradication due to the advent of effective vaccines. Highly active antiretroviral therapy is able to delay the onset of AIDS but can neither rid the body of HIV-1 proviral DNA nor prevent further transmission. A prophylactic vaccine that prevents the various mechanisms HIV-1 has to evade and attack our immune system is needed to end the HIV-1 pandemic. Recent advances in engineered nuclease systems, like the CRISPR/Cas9 system, have …

Ubr3, A Novel Modulator Of Hh Signaling Affects The Degradation Of Costal-2 And Kif7 Through Poly-Ubiquitination, Tongchao Li, Junkai Fan, Bernardo Blanco-Sánchez, Nikolaos Giagtzoglou, Guang Lin, Shinya Yamamoto, Manish Jaiswal, Kuchuan Chen, Jie Zhang, Wei Wei, Michael T. Lewis, Andrew K. Groves, Monte Westerfield, Jianhang Jia, Hugo J. Bellen

Markey Cancer Center Faculty Publications

Hedgehog (Hh) signaling regulates multiple aspects of metazoan development and tissue homeostasis, and is constitutively active in numerous cancers. We identified Ubr3, an E3 ubiquitin ligase, as a novel, positive regulator of Hh signaling in Drosophila and vertebrates. Hh signaling regulates the Ubr3-mediated poly-ubiquitination and degradation of Cos2, a central component of Hh signaling. In developing Drosophila eye discs, loss of ubr3 leads to a delayed differentiation of photoreceptors and a reduction in Hh signaling. In zebrafish, loss of Ubr3 causes a decrease in Shh signaling in the developing eyes, somites, and sensory neurons. However, not all tissues that require …

A Novel Variant In Cmah Is Associated With Blood Type Ab In Ragdoll Cats, Barbara Gandolfi, Robert Grahn, Nicholas Gustafson, Daniela Proverbio, Eva Spada, Badri Adhikari, Janling Cheng, Gordon Andrews, Leslie Lyons, Chris Helps

Computer Science Faculty Works

The enzyme cytidine monophospho-N-acetylneuraminic acid hydroxylase is associated with the production of sialic acids on cat red blood cells. The cat has one major blood group with three serotypes; the most common blood type A being dominant to type B. A third rare blood type is known as AB and has an unclear mode of inheritance. Cat blood type antigens are defined, with N-glycolylneuraminic acid being associated with type A and N-acetylneuraminic acid with type B. Blood type AB is serologically characterized by agglutination using typing reagents directed against both A and B epitopes. While a genetic characterization of blood …

The Foundations Of Network Dynamics In An Rna Recombinase System, Jessica Anne Mellor Yeates

Dissertations and Theses

How life originated from physical and chemical processes is one of the great questions still unanswered today. Studies towards this effort have transitioned from the notion of a single self-replicating entity to the idea that a network of interacting molecules made this initial biological leap. In order to understand the chemical kinetic and thermodynamic mechanisms that could engender pre-life type networks we present an empirical characterization of a network of RNA recombinase molecules. We begin with 1-, 2-, and 3-molecular ensembles and provide a game theoretic analysis to describe the frequency dependent dynamics of competing and cooperating RNA genotypes. This …

A Mutation In Ltbp2 Causes Congenital Glaucoma In Domestic Cats (Felis Catus), Markus H. Kuehn, Koren A. Lipsett, Marilyn Menotti-Raymond, S. Scott Whitmore, Todd E. Scheetz, Victor A. David, Stephen J. O'Brien, Zhongyuan Zhao, Jackie K. Jens, Elizabeth M. Snella, N. Matthew Ellinwood, Gillian J. Mclellan

Chemistry Faculty Publications

The glaucomas are a group of diseases characterized by optic nerve damage that together represent a leading cause of blindness in the human population and in domestic animals. Here we report a mutation in LTBP2 that causes primary congenital glaucoma (PCG) in domestic cats. We identified a spontaneous form of PCG in cats and established a breeding colony segregating for PCG consistent with fully penetrant, autosomal recessive inheritance of the trait. Elevated intraocular pressure, globe enlargement and elongated ciliary processes were consistently observed in all affected cats by 8 weeks of age. Varying degrees of optic nerve damage resulted by …

Novel Interactome Of Saccharomyces Cerevisiae Myosin Type Ii Identified By A Modified Integrated Membrane Yeast Two-Hybrid (Imyth) Screen, Ednalise Santiago, Pearl Akamine, Jamie Snider, Victoria Wong, Matthew Jessulat, Viktor Deineko, Alla Gagarinova, Hiroyuki Aoki, Zoran Minic, Sadhna Phanse, Andrea San Antonio, Luis A Cubano, Brian C. Rymond, Mohan Babu, Igor Stagljar, Jose R. Rodriguez-Medina

Biology Faculty Publications

Nonmuscle myosin type II (Myo1p) is required for cytokinesis in the budding yeast Saccharomyces cerevisiae. Loss of Myo1p activity has been associated with growth abnormalities and enhanced sensitivity to osmotic stress, making it an appealing antifungal therapeutic target. The Myo1p tail-only domain was previously reported to have functional activity equivalent to the full-length Myo1p whereas the head-only domain did not. Since Myo1p tail-only constructs are biologically active, the tail domain must have additional functions beyond its previously described role in myosin dimerization or trimerization. The identification of new Myo1p-interacting proteins may shed light on the other …

The Role Of Cellulose Synthase-Like D Genes In Tip Growth Of Physcomitrella Patens, Erin E. Killeavy, Arielle Chaves, Alison Roberts

Senior Honors Projects

Physcomitrella patens is a non-vascular plant with a relatively small genome and is amongst the few eukaryotic organisms that have a high rate of homologous recombination. This is valuable in biological research because it allows for targeted genetic modification of the organism. In vascular plants like Arabidopsis thaliana, a model organism, Cellulose Synthase-like D (CSLD) genes have been discovered to be important in tip growth. This type of growth is observed in the pollen tubes and root hairs of these plant types. The CSLD genes in Arabidopsis were found to play a crucial role in the growth of …

The Effect Of Transformed Escherichia Coli On The Mouse Intestine Microbiome: The Microbial Metabolic Enhancement Hypothesis, Bryar P. Kader

Senior Honors Theses

Metabolic disorders affect around thirty-four percent of the population in the United States. Among these disorders is lactose intolerance, which results from diminished production of the human lactase enzyme. This disorder and others like it are genetically determined and cannot be cured. However, the use of transformed bacteria implanted in the colon may provide a means by which the faulty pathway can be bypassed. To test whether transformed bacteria have the capability to aid in the digestion of normally indigestible compounds, a transformed strain of Escherichia coli overexpressing the beta-galactosidase enzyme encoded by the lacZ gene was colonized in the …

Nonreplicative Dna Helicases Involved In Maintaining Genome Stability, Salahuddin Syed

USF Tampa Graduate Theses and Dissertations

Double-strand breaks and stalled forks arise when the replication machinery encounters damage from exogenous sources like DNA damaging agents or ionizing radiation, and require specific DNA helicases to resolve these structures. Sgs1 of Saccharomyces cerevisiae is a member of the RecQ family of DNA helicases and has a role in DNA repair and recombination. The RecQ family includes human genes BLM, WRN, RECQL4, RECQL1, and RECQL5. Mutations in BLM, WRN, and RECQL4 result in genetic disorders characterized by developmental abnormalities and a predisposition to cancer. All RecQ helicases have common features including a …

Axonal Transport And Life Cycle Of Mitochondria In Parkinson's Disease Model, Hyun Sung

Open Access Dissertations

In neurons, normal distribution and selective removal of mitochondria are essential for preserving compartmentalized cellular function. Parkin, an E3 ubiquitin ligase associated with familial Parkinson’s disease, has been implicated in mitochondrial dynamics and removal. However, it is not clear how Parkin plays a role in mitochondrial turnover in vivo, and whether the mature neurons possess a compartmentalized Parkin-dependent mitochondrial life cycle. Using the live Drosophila nervous system, here, I investigate the involvement of Parkin in mitochondrial dynamics; organelle distribution, morphology and removal. Parkin deficient animals displayed less number of axonal mitochondria without disturbing organelle motility behaviors, morphology and metabolic state. …

Molecular Analysis Confirming The Introduction Of Nile Crocodiles, Crocodylus Niloticus Laurenti 1768 (Crocodylidae), In Southern Florida, With An Assessment Of Potential For Establishment, Spread, And Impacts., Michael R. Rochford, Kenneth L. Krysko, Frank J. Mazzotti, Matthew W. Shirley, Mark W. Parry, Joseph A. Wasilewski, Jeffrey S. Beauchamp, Christpher R. Gillette, Edward F. Metzger Iii, Michiko A. Squires, Louis A. Somma

Papers in Herpetology

The state of Florida, USA, has more introduced herpetofauna than any other governmental region on Earth. Four species of nonnative crocodilians have been introduced to Florida (all since 1960), one of which is established. Between 2000–2014 we field-collected three nonnative crocodilians in Miami-Dade County, Florida, and one in Hendry County, Florida. We used DNA barcoding and molecular phylogenetics to determine species identification and native range origin. Also, we described diet, movement, and growth for one crocodile. Our molecular analyses illustrated that two of the crocodiles we collected are most closely related to Nile Crocodiles (Crocodylus niloticus) from South Africa, suggesting …

Investigating The Roles And Interactions Of Sad-6 Within The Parameters Of Meiotic Silencing By Unpaired Dna ( Msud )., Zachary J. Smith

Theses and Dissertations

Meiotic silencing by unpaired DNA (MSUD) is a process observed in the model organism Neurospora crassa. During this process unpaired DNA between homologous chromosomes is detected and silenced, resulting in the suppression of unpaired genes. The effects of MSUD can be seen using phenotypic markers such as the Roundspore gene and evidence supports the existence of a physical search for unpaired DNA. However, the mechanism for detecting unpaired DNA remains uncertain. Previously, we have shown evidence that a Rad54-like protein, SAD-6 is required for the efficient completion of MSUD and may be necessary for the detection of unpaired DNA. Currently, …

A Mitochondrial Dna-Based Computational Model Of The Spread Of Human Populations, Peter Revesz

School of Computing: Faculty Publications

This paper presents a mitochondrial DNA-based computational model of the spread of human populations. The computation model is based on a new measure of the relatedness of two populations that may be both heterogeneous in terms of their set of mtDNA haplogroups. The measure gives an exponentially increasing weight for the similarity of two haplogroups with the number of levels shared in the mtDNA classification tree. In an experiment, the computational model is applied to the study of the relatedness of seven human populations ranging from the Neolithic through the Bronze Age to the present. The human populations included in …

Genomic Analysis Of Meiothermus Ruber Mrub_1907 And Meiothermus Ruber Mrub_1844 With Potential Ortholog Escherichia Coli B3774 Ilvc And Escherichia Coli B3771 Ilvc Gene Through Bioinformatics, Felipe A. Hernandez, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses the bioinformatics tools associated with the Guiding Education through Novel Investigation – Annotation Collaboration Toolkit (GENI-ACT) to predict gene function. We investigated the biological function of the genes Mrub_1907 and Mrub_1844. We predict that Mrub__1907 encodes the enzyme ketol-acid reductoisomerase (DNA coordinates 1966630..1967649 on the reverse strand), which is the fourth step of the L-isoleucine pathway (from threonine) (KEGG map number 00290). It catalyzes the conversion of (R)-3- Hydroxy-3-methyl-2-oxopentanoate to (R)-2-3 Dihydroxy-3-methylpentanoate. The E. coli K12 MG1655 ortholog is predicted to be b3774, which has the gene …

Comparing Meiothermus Ruber And Myxococcus Xanthus In The Purine Metabolism Pathway, Linnea J. Ritchie, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses the bioinformatics tools associated with the Guiding Education through Novel Investigation – Annotation Collaboration Toolkit (GENI-ACT) to predict gene function. I investigated the biological functions of Mrub_1053 Mrub_2281 and Mrub_2299. I predicted that Mrub_1053 and Mrub_2281 (DNA coordinates 1053364..1054359 on the forward strand and 2333172..2334113 on the forward strand respectively) encodes the enzyme phosphoribose-1-pyrophosphate synthetase (PRS) which is the first step of the purine synthesis pathway (KEGG). I also predicted that Mrub_2299 (DNA coordinates: 2352378..2353775 on the forward strand) encodes for Phosphoribosyl pyrophosphate (PRPP) amidotransferase, which is …

E. Coli B3639 And B3634 Are Orthologs Of Mrub_2047 And Mrub_1372, Rong Zheng, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses the bioinformatics tools associated with the Guiding Education through Novel Investigation –Annotation Collaboration Toolkit (GENI-ACT) to predict gene function. We investigated the biological function of the genes Mrub_2047 and Mrub_1372. We predict that Mrub_2047 encodes the enzyme fused 4'-phosphopantothenoylcysteine decarboxylase/phosphopantothenoylcysteine synthetase, FMN-binding (DNA coordinates 2083590..2084816 on the forward strand), which is the first and the second steps of the CoA biosynthesis pathway (KEGG map number 00770). It catalyzes the conversion of (R)-4’-phosphopantothenate to (R)-4’-phosphopantothenoyl-L-cysteine and the conversion of (R)-4’-phosphopantothenoyl-L-cysteine to 4’-phosphopantetheine. The E. coli K12 MG1655 ortholog …

Dna Sequencing Activity, Sarah O'Leary-Driscoll

Sequencing & Genome Mining

This activity is meant to introduce students to basic DNA sequencing techniques. Using a hands-on approach helps them understand the fundamentals of what is happening in the lab, and the questions that accompany the activity can lead to more in depth discussions about sequencing, and the development of the next generation sequencing techniques.

Interactions Of Two Large Antiviral Polyamides With The Long Control Region Of Hpv16., Elena Vasilieva, Jacquelyn Niederschulte, Yang Song, George Harris, Kevin Koeller, Puhong Liao, James Bashkin, Cynthia Dupureur

Chemistry & Biochemistry Faculty Works

No abstract provided.

And-1 Is Required For Homologous Recombination Repair By Regulating Dna End Resection, Yongming Li, Zongzhu Li, Zhiyong Han, Wenge Zhu

Biochemistry and Molecular Medicine Faculty Publications

Homologous recombination (HR) is a major mechanism to repair DNA double-strand breaks (DSBs). Although tumor suppressor CtIP is critical for DSB end resection, a key initial event of HR repair, the mechanism regulating the recruitment of CtIP to DSB sites remains largely unknown. Here, we show that acidic nucleoplasmic DNA‐binding protein 1 (And‐1) forms complexes with CtIP as well as other repair proteins, and is essential for HR repair by regulating DSB end resection. Furthermore, And-1 is recruited to DNA DSB sites in a manner dependent on MDC1, BRCA1 and ATM, down-regulation of And-1 impairs end resection by reducing the …

Effective Drug Treatment Induces Drug Resistance Through Rapid Genome Alteration-Mediated Cancer Evolution, Steven Horne

Wayne State University Dissertations

The central paradox associated with current cancer therapeutic strategies is initially effective treatment, which eliminates a high tumor cell count, consistently results in successful drug resistance. Mathematical and evolutionary modeling have previously suggested that therapeutic intervention could provide selective pressure for the expansion of resistant variants. Drug-related stress has been associated with genome chaos, a common phenomenon in cancer characterized as rapid, stochastic genomic fragmentation and reorganization. Since cancer represents an evolutionary process, analysis within the context of genome-mediated cancer evolution can shed light on this key problem of therapeutics. We propose that genomic change is a general response to …

A Novel Role For Repetitive Sequences In Recognition Of The Drosophila Melanogaster X Chromosome, Sonal Suresh Joshi

Wayne State University Dissertations

In humans and fruit flies, males have one X chromosome while females have two. This imbalance in gene dosage is potentially lethal, and the process of dosage compensation corrects it. The MSL (Male Specific Lethal) complex, which is composed of five proteins and one of two functionally redundant long non-coding roX (RNA on the X) RNAs, brings about dosage compensation in Drosophila melanogaster. In fruit fly dosage compensation, all the genes on the single male X chromosome are upregulated approximately twofold, via chromatin modifications, to equalize gene dosage with the two X chromosomes of females. This process calls for highly …

An Analysis Of The Interaction Between Sin3 And Methionine Metabolism In Drosophila, Mengying Liu

Wayne State University Dissertations

Chromatin modification and cellular metabolism are tightly connected. The mechanism for this cross-talk, however, remains incompletely understood. SIN3 controls histone acetylation through association with the histone deacetylase RPD3. In this study, my major goal is to explore the mechanism of how SIN3 regulates cellular metabolism.

Methionine metabolism generates the major methyl donor S-adenosylmethionine (SAM) for histone methylation. In collaboration with others, I report that reduced levels of some enzymes involved in methionine metabolism and histone demethylases lead to lethality, as well as wing development and cell proliferation defects in Drosophila melanogaster. Additionally, disruption of methionine metabolism can directly affect histone …

Modeling The Mechanism Underlying Environmental And Genetic Determinants Of Gene Expression And Complex Traits, Gregory Alan Moyerbrailean

Wayne State University Dissertations

Advances in next-generation sequencing technologies and functional genomics strategies have allowed researchers to identify both common and rare genetic variation, to deeply profile gene expression, and even to determine regions of active gene transcription.

While these technologies and strategies have contributed greatly to our understanding of complex traits and diseases, there are many biological questions and analytical issues to be addressed.

Genome-wide association studies (GWAS) have successfully identified large numbers of genetic variants associated with complex traits and diseases. However, in many cases the mechanistic link between the phenotype and associated variant remains unclear. This may be because most variants …