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Articles 1 - 30 of 120
Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Molecular And Structural Basis For Replication Initiation And Strand Separation By Human Mitochondrial Dna Polymerase Γ, Viktoriia Sokolova, Gina Buchel, S. Strock, Ashok R. Nayak, Dmitry Temiakov
Molecular And Structural Basis For Replication Initiation And Strand Separation By Human Mitochondrial Dna Polymerase Γ, Viktoriia Sokolova, Gina Buchel, S. Strock, Ashok R. Nayak, Dmitry Temiakov
Department of Biochemistry and Molecular Biology Faculty Papers
Defects in human mitochondrial DNA (mtDNA) replication can lead to somatic mutations associated with a range of devastating mitochondrial diseases. However, the molecular mechanisms governing the earliest steps of mtDNA replication and their fidelity remain poorly understood. Here, we found that DNA polymerase gamma (Polγ) forms stable complexes with RNA-DNA primer-template substrates, exhibiting greater stability and lower misincorporation than on DNA-primed substrates. Structural analysis revealed that Polγ interacts with the 2'-OH groups of ribose within the first four nucleotides of the primer, explaining the stability of complexes that utilize RNA primers. Although Polγ requires TWINKLE to extend RNA primers, its …
Three-Dimensional Chromatin Architecture Is Rapidly Restored After Dna Replication, Tyler K. Fenstermaker, Svetlana Petruk, Alexander Mazo
Three-Dimensional Chromatin Architecture Is Rapidly Restored After Dna Replication, Tyler K. Fenstermaker, Svetlana Petruk, Alexander Mazo
Department of Biochemistry and Molecular Biology Faculty Papers
Studies of post-replicative chromatin exclusively focus on the kinetics of protein binding after DNA replication to understand maintenance of transcriptional programs. Here we investigated both chromatin-bound factors and the three-dimensional architecture of the post-replicative genome in human cells. We found that transcription factors and chromatin looping proteins rapidly associate with nascent DNA. We discovered that the architectural factors, CTCF and YY1, bind to their target sequences immediately following DNA replication, and that chromatin loops from 39 to 425 kb re-form within 10 min of DNA replication. This suggests that the 3D structure of chromatin is at most briefly disrupted by …
Sensing Rna’S Conformation With A Solid-State Nanopore Device At Various Ph And Temperature, Haopeng Li
Sensing Rna’S Conformation With A Solid-State Nanopore Device At Various Ph And Temperature, Haopeng Li
Graduate Theses and Dissertations
This study uses solid-state nanopore technology to investigate the stability and dynamics of RNA molecules under thermal stress and pH fluctuations. Two distinct mRNA samples were analyzed: (1) heat shock protein (HSP)-encoding mRNA extracted from Sulfolobus solfataricus P2, a thermophilic archaeon inhabiting extreme environments such as geothermal sulfuric hot springs (pH < 4, temperature range: 65–90°C), and (2) total RNA extracted from White Leghorn chickens, which thrive under standard physiological conditions. ΦX174 virion single-stranded DNA (ssDNA) were included as a comparative reference. Nanopores, fabricated in silicon nitride membranes, were used to electrically characterize the structural properties of individual RNA molecules in solution, close to their native environments. The nanopore membrane separates two chambers containing salt buffer solution, where ionic current is the primary measurement parameter. When a voltage bias is applied across the membrane, ion flow and an ionic current can be measured. Charged RNA molecules driven translocation through the nanopore induces pore resistance changes, resulting in detectable current blockade events. Variations in these events provide insights into RNA secondary structure and conformational dynamics. By systematically altering pH and temperature, this study elucidates the effects of environmental stressors on RNA stability and structural integrity. The findings reveal distinct responses between thermophilic HSP-encoding mRNA and mesophilic RNA, underscoring the adaptive mechanisms of thermophilic RNA under extreme conditions. These results contribute to a better understanding of RNA behavior under stress and establish a foundation for future applications in RNA-based diagnostics and biotechnology development.
Maternal Inflammation Alters Nuclear And Mitochondrial Dna Methylation Patterns In Neonatal Brain Monocytes, Andrew Ebenezer, Jonathan Hicks, Brooke Hollander, Alexander Hone, Mona Batish, Robert Akins, Adam Marsh, Elizabeth Wright-Jin
Maternal Inflammation Alters Nuclear And Mitochondrial Dna Methylation Patterns In Neonatal Brain Monocytes, Andrew Ebenezer, Jonathan Hicks, Brooke Hollander, Alexander Hone, Mona Batish, Robert Akins, Adam Marsh, Elizabeth Wright-Jin
Department of Medicine Faculty Papers
Neonatal hypoxic ischemic encephalopathy (HIE) is a common birth complication that can cause death or lifelong disabling conditions like cerebral palsy, epilepsy, and autism. It is well established that maternal infection and inflammation are significant risk factors for HIE but reasons for this increase in neurological risk to the offspring remain unknown. Inflammation or infection are associated with epigenetic changes and may contribute to the increased risk of neurodevelopmental disability in exposed offspring. Here, we analyzed and compared DNA methylation patterns in brain monocytes isolated from control, maternal immune activation (MIA), and an inflammation sensitized HIE (IS-HIE) CF-1 mouse model …
Investigating Rad14 Gene Nucleotide Excision Repair On G-Quadruplexes, Juan Pablo Olvera Rodriguez, Tyna Trevino, Yvette Gonzalez, Georgia Romike
Investigating Rad14 Gene Nucleotide Excision Repair On G-Quadruplexes, Juan Pablo Olvera Rodriguez, Tyna Trevino, Yvette Gonzalez, Georgia Romike
Posters - 2026
DNA is typically found as a double-stranded helical structure; however, it can be found in different types of structures, such as G-quadruplexes (G4s). These are structures formed when DNA sequences are rich in Guanines, which interact with each other by hydrogen bonding, forming stacked G-tetrads. These guanine-rich structures are known for interacting with DNA during important cell processes, such as recombination and replication, leading to instability and DNA damage (Grey et al., 2014). If not treated properly, these structures may contribute to mutations and cancer development. To solve these issues, cells have developed maintenance pathways such as Nucleotide Excision Repair …
Nucleotide Excision Repair In Yeast, Kinleigh Mines, Larry Ramirez, Jacob Rodriguez, Delynda Gonzalez
Nucleotide Excision Repair In Yeast, Kinleigh Mines, Larry Ramirez, Jacob Rodriguez, Delynda Gonzalez
Posters - 2026
DNA damage occurs constantly in cells due to environmental factors and normal cellular processes, making DNA repair pathways essential for maintaining genomic stability (Hindi et al., 2021). One major repair mechanism is Nucleotide Excision Repair (NER), which is responsible for recognizing and removing bulky DNA lesions that distort the double helix structure (Scharer, 2013). In Saccharomyces cerevisiae (yeast), the RAD14 gene plays a critical role in this pathway by helping identify and initiate repair of damaged DNA (Scharer, 2013). Another source of instability comes from the formation of G-quadruplex (G4) structures, which are secondary DNA configurations that can interfere with …
G-Quadruplex Dna-Driven Genomic Instability Under Ber Loss, Addison Belick, Claryssa Gutierrez, Joslynn Rosas, Andrea Vargas
G-Quadruplex Dna-Driven Genomic Instability Under Ber Loss, Addison Belick, Claryssa Gutierrez, Joslynn Rosas, Andrea Vargas
Posters - 2026
Base Excision Repair (BER) is a cellular tool that can repair damaged DNA (Hindi et al., 2022, Cellular and Molecular Life Sciences). G-quadruplexes (G4s) are unique 4-stranded structures in DNA or RNA that are rich in guanine (Gray et al., 2023, Nat. Chem. Biol). The purpose of this study is to understand whether BER contributes to the removal of G4s in DNA. This will determine if the BER-deficient yeast is more sensitive to treatment with G4-binding drugs than the BER-proficient yeast. We will replace the APN1 gene in the yeast genome with the URA3 gene, because the wild type yeast …
Exploring Base Excision Repair Using Gene Knockout, Gregory Guantos, Cailyn Brock, Kamily Visser, Dylan Vargas
Exploring Base Excision Repair Using Gene Knockout, Gregory Guantos, Cailyn Brock, Kamily Visser, Dylan Vargas
Posters - 2026
• Base Excision Repair (BER) fixes damaged 3DNA bases throughout the cell cycle by removing damaged bases and replacing either one nucleotide in short-patch BER or a short stretch of nucleotides in long-patch BER. (Hindi, 2021, Cellular and Molecular Life Sciences:CMLS)
• 4G-quadruplexes (G4s) are 4 stranded secondary DNA structures formed in guanine rich areas of DNA and RNA. (Rhodes, 2015, Nucleic Acids Research)
The URA3 plasmid was used as a PCR template to make a gene deletion construct, then yeast were transformed so APN1 was replaced by URA3. 2APN1 encodes a major DNA repair enzyme in yeast, and strains …
Multicomponent Deoxyribozyme Probes For Targeted Detection Of Cancer Associated Gene Insertions, Samuel R. Veleke
Multicomponent Deoxyribozyme Probes For Targeted Detection Of Cancer Associated Gene Insertions, Samuel R. Veleke
Honors Undergraduate Theses
Insertions and deletions (indels) in DNA sequences of genes are linked with cancers such as glioblastoma (GB). Thus, indels may be used as potential cancer biomarkers. In the NANOG gene, its pseudogene NANOGP8 has a 22 base pair insertion sequence for GB patients. In this work, the NANOG gene and the insertion sequence were detected in one sample using a dual-fluorescent assay containing two multicomponent split deoxyribozyme (Dz) probe complexes. One complex used TXR fluorescence to detect the gene regardless of the insertion’s presence. The other complex used fluorescein (FAM) fluorophore to detect the insertion. The probes were able to …
31p Solution Nmr Investigation Of Abasic Dna, Clarissa R. Krimmel
31p Solution Nmr Investigation Of Abasic Dna, Clarissa R. Krimmel
Graduate Theses/Dissertations
Base excision repair (BER) mechanisms fix single base lesions in DNA, such as T:G mismatches. During the base excision repair mechanism, an abasic site (AP site) is formed as an intermediate. AP sites are unstable and highly mutagenic; they can stop DNA replication. This research investigates how the conformational properties of abasic sites in DNA affect the binding recognition of enzymes involved in DNA repair mechanisms, including BER. Three different abasic sequences are being analyzed for this research project. A second project looks at the effects of a naturally occurring purine derivative, hypoxanthine, on the DNA backbone. These hypoxanthine lesions …
Dna Extrusion Size Determines Pathway Choice During Cag Repeat Expansion, Mayuri Bhatia, Ashutosh S. Phadte, Anna Lakhina, Anthony R. Monte Carloi Iii, Sarah Barndt, Anna Pluciennik
Dna Extrusion Size Determines Pathway Choice During Cag Repeat Expansion, Mayuri Bhatia, Ashutosh S. Phadte, Anna Lakhina, Anthony R. Monte Carloi Iii, Sarah Barndt, Anna Pluciennik
Department of Biochemistry and Molecular Biology Faculty Papers
DNA triplet repeat expansion causes several primarly neurological disorders like Huntington's disease, myotonic dystrophy type 1, and fragile-X related disorders. There is general consensus that recognition of extrahelical extrusions or hairpin-loop structures (formed by strand slippage) by the DNA mismatch repair protein MutSβ leads to repeat expansion by a mutagenic process. By contrast, the FAN1 nuclease attenuates triplet repeat expansion, the molecular basis of which was explained by our recent finding that FAN1 nuclease cleaves and initiates removal of extrahelical extrusions. Here we show that extrusions containing two or more triplet repeats are subject to recognition and processing by either …
The Effects Of Tfeα And Promoter Sequence On Early Events In Archaeal Transcription Initiation, Madolyn Toli
The Effects Of Tfeα And Promoter Sequence On Early Events In Archaeal Transcription Initiation, Madolyn Toli
Dissertations and Theses
Expression of genes is dependent on promoter sequences in DNA, which direct transcription by RNA polymerase. Transcription factors interact with promoters and RNAP and are often conserved and are essential for proper gene expression. In this thesis, a functional region of archaeal TFEα, homologous to eukaryotic TFIIEα, has been identified, and specific amino acids in these regions have been determined to have significant importance in TFEα's ability to promote transcription in early initiation. All three Domains of life encode a 16S rRNA promoter, which is responsible for production of the 16S portion of ribosome. Transcription with this promoter is not …
Ion-Dna Interactions As A Key Determinant Of Uracil Dna Glycosylase Activity., Sharon N Greenwood, Alexis N Dispensa, Matthew Wang, Justin R Bauer, Timothy D Vaden, Zhiwei Liu, Brian P Weiser
Ion-Dna Interactions As A Key Determinant Of Uracil Dna Glycosylase Activity., Sharon N Greenwood, Alexis N Dispensa, Matthew Wang, Justin R Bauer, Timothy D Vaden, Zhiwei Liu, Brian P Weiser
Rowan-Virtua School of Osteopathic Medicine Departmental Research
Because of their ubiquitous presence, ions interact with numerous macromolecules in the cell and affect critical biological processes. Here, we discuss how cations including Mg2+ alter the enzymatic activity of a DNA glycosylase by tuning its affinity for DNA. The response of uracil DNA glycosylase (UNG2) to Mg2+ ions in solution is biphasic and paradoxical, where low concentrations of the ion stimulate the enzyme, but high concentrations inhibit the enzyme. We analyzed this phenomenon by modeling experimental data with a statistical framework that we empirically derived to understand molecular systems that display biphasic behaviors. Parameters from our statistical …
Structural Basis For Intrinsic Strand Displacement Activity Of Mitochondrial Dna Polymerase, Ashok Nayak, Viktoriia Sokolova, Sirelin Sillamaa, Karl Herbine, Juhan Sedman, Dmitry Temiakov
Structural Basis For Intrinsic Strand Displacement Activity Of Mitochondrial Dna Polymerase, Ashok Nayak, Viktoriia Sokolova, Sirelin Sillamaa, Karl Herbine, Juhan Sedman, Dmitry Temiakov
Department of Biochemistry and Molecular Biology Faculty Papers
Members of the Pol A family of DNA polymerases, found across all domains of life, utilize various strategies for DNA strand separation during replication. In higher eukaryotes, mitochondrial DNA polymerase γ relies on the replicative helicase TWINKLE, whereas the yeast ortholog, Mip1, can unwind DNA independently. Using Mip1 as a model, we present a series of high-resolution cryo-EM structures that capture the process of DNA strand displacement. Our data reveal previously unidentified structural elements that facilitate the unwinding of the downstream DNA duplex. Yeast cells harboring Mip1 variants defective in strand displacement exhibit impaired oxidative phosphorylation and loss of mtDNA, …
Evaluation Of The Dnazyme Gr5 For The Determination Of Lead Speciation In Natural Waters, Gaganprit Gill
Evaluation Of The Dnazyme Gr5 For The Determination Of Lead Speciation In Natural Waters, Gaganprit Gill
Theses and Dissertations (Comprehensive)
This thesis explores the development and application of a DNAzyme-based biosensor designed to detect labile metal species in environmental samples. Real time and on-site monitoring of labile metal fractions would make a valuable contribution to environmental management, as these fractions are the most bioavailable and pose significant toxicity risks to aquatic organisms. Conventional methods for detecting labile metals, while effective, are often burdened by high costs, complexity, and lengthy processing times, making them less ideal for rapid and widespread environmental assessments.
The first manuscript of this thesis (chapter 2) establishes the fundamental capabilities of the Pb2+-specific DNAzyme GR5 …
The C-Terminal 4cxxc-Type Zinc Finger Domain Of Cdca7 Recognizes Hemimethylated Dna And Modulates Activities Of Chromatin Remodeling Enzyme Hells, Akeo Shinkai, Hideharu Hashimoto, Chikako Shimura, Hiroaki Fujimoto, Kei Fukuda, Naoki Horikoshi, Masaki Okano, Hitoshi Niwa, Erik W Debler, Hitoshi Kurumizaka, Yoichi Shinkai
The C-Terminal 4cxxc-Type Zinc Finger Domain Of Cdca7 Recognizes Hemimethylated Dna And Modulates Activities Of Chromatin Remodeling Enzyme Hells, Akeo Shinkai, Hideharu Hashimoto, Chikako Shimura, Hiroaki Fujimoto, Kei Fukuda, Naoki Horikoshi, Masaki Okano, Hitoshi Niwa, Erik W Debler, Hitoshi Kurumizaka, Yoichi Shinkai
Department of Biochemistry and Molecular Biology Faculty Papers
The chromatin-remodeling enzyme helicase lymphoid-specific (HELLS) interacts with cell division cycle-associated 7 (CDCA7) on nucleosomes and is involved in the regulation of DNA methylation in higher organisms. Mutations in these genes cause immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome, which also results in DNA hypomethylation of satellite repeat regions. We investigated the functional domains of human CDCA7 in HELLS using several mutant CDCA7 proteins. The central region is critical for binding to HELLS, activation of ATPase, and nucleosome sliding activities of HELLS-CDCA7. The N-terminal region tends to inhibit ATPase activity. The C-terminal 4CXXC-type zinc finger domain contributes to CpG …
Computational Analysis Of O6-Methylated Guanine And Thioguanine Complexes, Kirsten Stinson, Michael Bowman
Computational Analysis Of O6-Methylated Guanine And Thioguanine Complexes, Kirsten Stinson, Michael Bowman
Lux et Fides: A Journal for Undergraduate Christian Scholars
DNA methylation occurring on the O6 position of guanine has been linked to the formation of cancer. DNA complexes with O6-methylated guanine have been studied experimentally, yet questions remain concerning the carcinogenic properties of O6-methylguanine. This present research explored the interaction between O6-methylguanine and its potential nucleobase pairs of cytosine and adenine in hopes of elucidating the mutagenic characteristics of O6-methylguanine. A variety of computational methods including Density Functional Theory (DFT), Symmetry Adapted Perturbation Theory (SAPT), Noncovalent Interaction (NCI) analysis, and Natural Bond Orbital (NBO) analysis were employed to comprehensively probe …
Discovery Of A Small-Molecule Inhibitor That Traps Polθ On Dna And Synergizes With Parp Inhibitors, William Fried, Mrityunjay Tyagi, Leonid Minakhin, Gurushankar Chandramouly, Taylor Tredinnick, Mercy Ramanjulu, William Auerbacher, Marissa L Calbert, Timur Rusanov, Trung Hoang, Nikita Borisonnik, Robert Betsch, John Krais, Yifan Wang, Umeshkumar Vekariya, John Gordon, George Morton, Tatiana Kent, Tomasz Skorski, Neil Johnson, Wayne Childers, Xiaojiang Chen, Richard Pomerantz
Discovery Of A Small-Molecule Inhibitor That Traps Polθ On Dna And Synergizes With Parp Inhibitors, William Fried, Mrityunjay Tyagi, Leonid Minakhin, Gurushankar Chandramouly, Taylor Tredinnick, Mercy Ramanjulu, William Auerbacher, Marissa L Calbert, Timur Rusanov, Trung Hoang, Nikita Borisonnik, Robert Betsch, John Krais, Yifan Wang, Umeshkumar Vekariya, John Gordon, George Morton, Tatiana Kent, Tomasz Skorski, Neil Johnson, Wayne Childers, Xiaojiang Chen, Richard Pomerantz
Department of Biochemistry and Molecular Biology Faculty Papers
The DNA damage response (DDR) protein DNA Polymerase θ (Polθ) is synthetic lethal with homologous recombination (HR) factors and is therefore a promising drug target in BRCA1/2 mutant cancers. We discover an allosteric Polθ inhibitor (Polθi) class with 4-6 nM IC50 that selectively kills HR-deficient cells and acts synergistically with PARP inhibitors (PARPi) in multiple genetic backgrounds. X-ray crystallography and biochemistry reveal that Polθi selectively inhibits Polθ polymerase (Polθ-pol) in the closed conformation on B-form DNA/DNA via an induced fit mechanism. In contrast, Polθi fails to inhibit Polθ-pol catalytic activity on A-form DNA/RNA in which the enzyme binds in …
Parp2 Promotes Break Induced Replication-Mediated Telomere Fragility In Response To Replication Stress, Daniela Muoio, Natalie Laspata, Rachel L Dannenberg, Caroline Curry, Simone Darkoa-Larbi, Mark Hedglin, Shikhar Uttam, Elise Fouquerel
Parp2 Promotes Break Induced Replication-Mediated Telomere Fragility In Response To Replication Stress, Daniela Muoio, Natalie Laspata, Rachel L Dannenberg, Caroline Curry, Simone Darkoa-Larbi, Mark Hedglin, Shikhar Uttam, Elise Fouquerel
Department of Biochemistry and Molecular Biology Faculty Papers
PARP2 is a DNA-dependent ADP-ribosyl transferase (ARTs) enzyme with Poly(ADP-ribosyl)ation activity that is triggered by DNA breaks. It plays a role in the Base Excision Repair pathway, where it has overlapping functions with PARP1. However, additional roles for PARP2 have emerged in the response of cells to replication stress. In this study, we demonstrate that PARP2 promotes replication stress-induced telomere fragility and prevents telomere loss following chronic induction of oxidative DNA lesions and BLM helicase depletion. Telomere fragility results from the activity of the break-induced replication pathway (BIR). During this process, PARP2 promotes DNA end resection, strand invasion and BIR-dependent …
Chemical Synthesis Of Sensitive Dna, Komal Chillar
Chemical Synthesis Of Sensitive Dna, Komal Chillar
Dissertations, Master's Theses and Master's Reports
Over the past decades, researchers have tried various chemical methods to synthesize modified oligodeoxynucleotides (ODNs, i.e. short segments of DNAs). Traditional ODN synthesis methods require strong basic, and nucleophilic conditions for the deprotection and cleavage of the ODN from the solid support. However, the sensitive ODNs containing labile functionalities are vulnerable to such harsh conditions. Sensitive ODNs have a wide range of applications in research and pharmaceuticals. To synthesize sensitive ODNs, researchers devised different strategies but no practical methods have been developed. To overcome these challenges, we developed alkyl Dim alkyl Dmoc technology. This innovative technology uses weakly basic and …
Structural Basis For Dna Proofreading, Gina Buchel, Ashok Nayak, Karl Herbine, Azadeh Sarfallah, Viktoriia Sokolova, Angelica Zamudio-Ochoa, Dmitry Temiakov
Structural Basis For Dna Proofreading, Gina Buchel, Ashok Nayak, Karl Herbine, Azadeh Sarfallah, Viktoriia Sokolova, Angelica Zamudio-Ochoa, Dmitry Temiakov
Department of Biochemistry and Molecular Biology Faculty Papers
DNA polymerase (DNAP) can correct errors in DNA during replication by proofreading, a process critical for cell viability. However, the mechanism by which an erroneously incorporated base translocates from the polymerase to the exonuclease site and the corrected DNA terminus returns has remained elusive. Here, we present an ensemble of nine high-resolution structures representing human mitochondrial DNA polymerase Gamma, Polγ, captured during consecutive proofreading steps. The structures reveal key events, including mismatched base recognition, its dissociation from the polymerase site, forward translocation of DNAP, alterations in DNA trajectory, repositioning and refolding of elements for primer separation, DNAP backtracking, and displacement …
Evaluation Of Potential Role Of R-Loop And G-Quadruplex Dna In The Fragility Of C-Myc During Chromosomal Translocation Associated With Burkitt's Lymphoma, Nitu Kumari, Kohal Das, Shivangi Sharma, Sumedha Dahal, Sagar Sanjiv Desai, Urbi Roy, Anju Sharma, Meghana Manjunath, Vidya Gopalakrishnan, S T Retheesh, Saniya M Javadekar, Bibha Choudhary, Sathees C Raghavan
Evaluation Of Potential Role Of R-Loop And G-Quadruplex Dna In The Fragility Of C-Myc During Chromosomal Translocation Associated With Burkitt's Lymphoma, Nitu Kumari, Kohal Das, Shivangi Sharma, Sumedha Dahal, Sagar Sanjiv Desai, Urbi Roy, Anju Sharma, Meghana Manjunath, Vidya Gopalakrishnan, S T Retheesh, Saniya M Javadekar, Bibha Choudhary, Sathees C Raghavan
Faculty, Staff and Student Publications
t(8;14) translocation is the hallmark of Burkitt's lymphoma and results in c-MYC deregulation. During the translocation, c-MYC gene on chromosome 8 gets juxtaposed to the Ig switch regions on chromosome 14. Although the promoter of c-MYC has been investigated for its mechanism of fragility, little is known about other c-MYC breakpoint regions. We have analyzed the translocation break points at the exon 1/intron 1 of c-MYC locus from patients with Burkitt's lymphoma. Results showed that the breakpoint region, when present on a plasmid, could fold into an R-loop confirmation in a transcription-dependent manner. Sodium bisulfite modification assay revealed significant single-strandedness …
Rna World And The Development Of Rna Protocells, Benjamin C. Mayfield
Rna World And The Development Of Rna Protocells, Benjamin C. Mayfield
PANDION: The Osprey Journal of Research and Ideas
Origins of life research, also known as pre-biotic chemistry or astrobiology, aims to unravel the mystery of the first cell’s origin on Earth. This interdisciplinary field encompasses biology, chemistry, and physics, with the primary goal of understanding the conditions necessary for life to emerge from abiotic environments. The RNA world hypothesis suggests that early life initially used RNA instead of DNA to store genomic information and for enzymatic functions. Protocells, membrane-bound entities with metabolic processes and self-replication capabilities, likely preceded the emergence of true cells. The challenges associated with RNA world is currently an active field of research. Advancements in …
Effects Of Group Ii Metal Binding On The Stability Of Dna I-Motif Structures, Charlotte Powers
Effects Of Group Ii Metal Binding On The Stability Of Dna I-Motif Structures, Charlotte Powers
Honors Theses
B-form DNA can adopt alternative structures while in superhelical duress. Alternative DNA structures are favored when there is an asymmetric distribution on complementary DNA strands. Cytosine rich strands may utilize cytosine-cytosine base pairing to form a four-stranded structure known as the i-motif (iM). The stability of iMs is affected by several factors such as DNA sequence, temperature, pH, ionic strength of the solution, and crowded conditions. While the effects of temperature, pH, and crowding conditions on iM stability have been well documented, the effects of ion presence in a solution has been less studied. Hence, those studies are the basis …
Exploring The Interaction Of Minor-Groove-Binder Netropsin With Dna Using Optical Tweezers, Irbazhusain Shaikh
Exploring The Interaction Of Minor-Groove-Binder Netropsin With Dna Using Optical Tweezers, Irbazhusain Shaikh
Honors Program Theses and Projects
Netropsin is an antibiotic that binds in the minor grooves of DNA, which also exhibits anticancer properties. There have been many previous studies that explored the binding of this drug to DNA using traditional methods where an ensemble averaging is used. In this study we explore the interaction of Netropsin with DNA at a single molecule level using dual beam optical tweezers. We trapped and stretched a single DNA molecule using optical tweezers to measure the force experienced by the DNA as a function of extension in the absence and presence of various concentrations of Netropsin. Our results show the …
Role Of Cdx4 And Sp5l In Zebrafish Development, Wesley Tsai
Role Of Cdx4 And Sp5l In Zebrafish Development, Wesley Tsai
Honors Theses
The Caudal Type Homeobox transcription factors cdx are a family of genes found in vertebrates that regulates body regionalization and anterior-posterior patterning. They are also responsible for regulating axial elongation, but the mechanisms behind this behavior are not known. Previous studies in mouse embryonic stem cells have shown that the cdx genes are necessary for upregulating the gene sp5 which may be linked to axial elongation. Sp5 is a zinc-finger transcription factor belonging to the specificity protein (sp) family. Our group has used in-situ hybridization experiments on zebrafish embryos to show that sp5-like (sp5l) is transcribed within tailbud tissues that …
Dpc29 Promotes Post-Initiation Mitochondrial Translation In Saccharomyces Cerevisiae, Kyle A. Hubble, Michael F. Henry
Dpc29 Promotes Post-Initiation Mitochondrial Translation In Saccharomyces Cerevisiae, Kyle A. Hubble, Michael F. Henry
Rowan-Virtua School of Osteopathic Medicine Departmental Research
Mitochondrial ribosomes synthesize essential components of the oxidative phosphorylation (OXPHOS) system in a tightly regulated process. In the yeast Saccharomyces cerevisiae, mitochondrial mRNAs require specific translational activators, which orchestrate protein synthesis by recognition of their target gene's 5'-untranslated region (UTR). Most of these yeast genes lack orthologues in mammals, and only one such gene-specific translational activator has been proposed in humans-TACO1. The mechanism by which TACO1 acts is unclear because mammalian mitochondrial mRNAs do not have significant 5'-UTRs, and therefore must promote translation by alternative mechanisms. In this study, we examined the role of the TACO1 orthologue in yeast. We …
Probing Amyloid-Beta Protein Structure And Dynamics With A Selective Antibody, Shikha Grover
Probing Amyloid-Beta Protein Structure And Dynamics With A Selective Antibody, Shikha Grover
Dissertations
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. The AD brain is characterized by significant neuronal loss and accumulation of insoluble fibrillar amyloid-β protein (Aβ) plaques and tau protein neurofibrillary tangles in the brain. However, over the last decade, many studies have shown that the neurodegenerative effect of Aβ may in fact be caused by various soluble oligomeric forms as opposed to the insoluble fibrils. Furthermore, the data suggest that a pre-fibrillar aggregated form, termed protofibrils, mediates direct neurotoxicity, and triggers a robust neuroinflammatory response.
Antibodies targeting the various conformation of Aβ are important therapeutic agents to prevent the progression …
Impact Of Sample Conditions On Dna Phosphodiester Backbone Bi/Bii Conformational Equilibrium Dynamics, Autumn C. Pilarski
Impact Of Sample Conditions On Dna Phosphodiester Backbone Bi/Bii Conformational Equilibrium Dynamics, Autumn C. Pilarski
Graduate Theses/Dissertations
DNA damage, such as single base lesions and mismatches, is highly prevalent within cells. If these DNA damage events are not repaired, they could lead to mutations and thus disease and cancer. Intricate repair mechanisms are in place to fix these damage events, one such being Base Excision Repair (BER) and associated enzyme: Thymine DNA Glycosylase (TDG). The first step of this repair process, recognition of the lesion by TDG, is not well understood. The following thesis presents results to better understand the fundamental biophysical question of how a DNA lesion within a mismatch context is recognized in a million …
Functional Characterization Of The Newly Discovered Type V Crispr-Cas Protein Cas12a2, Dylan J. Keiser
Functional Characterization Of The Newly Discovered Type V Crispr-Cas Protein Cas12a2, Dylan J. Keiser
All Graduate Theses and Dissertations, Spring 1920 to Summer 2023
Similarly to people, bacteria are under the treat of infection by viruses. To circumvent these threats, bacteria evolve complex immune systems. Our understanding of some of these immune systems has led to many advancements in the field of Biotechnology including tools that made expressing proteins for study in a lab easier, tools that revolutionized the feasibility of gene editing, and tools that could change the way we think about viral diagnostics and cancer therapeutics. A certain type of immune system that bacteria use to fight virus is called a CRISPR system. Presented here is work to understand the function of …