Genetics and Genomics Commons^™

Gaw20: Methods And Strategies For The New Frontiers Of Epigenetics And Pharmacogenomics, Nathan L. Tintle, David W. Fardo, Marzia De Andrade, Stella Aslibekyan, Julia N. Bailey, Justo Lorenzo Bermejo, Rita M. Cantor, Saurabh Ghosh, Philip Melton, Xuexua Wang, Jean W. Maccluer, Laura Almasy

Biostatistics Faculty Publications

GAW20 provided a platform for developing and evaluating statistical methods to analyze human lipid-related phenotypes, DNA methylation, and single-nucleotide markers in a study involving a pharmaceutical intervention. In this article, we present an overview of the data sets and the contributions analyzing these data. The data, donated by the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) investigators, included data from 188 families (N = 1105) which included genome-wide DNA methylation data before and after a 3-week treatment with fenofibrate, single-nucleotide polymorphisms, metabolic syndrome components before and after treatment, and a variety of covariates. The contributions from individual …

Association Analyses Of Repeated Measures On Triglyceride And High-Density Lipoprotein Levels: Insights From Gaw20, Saurabh Ghosh, David W. Fardo

Biostatistics Faculty Publications

Background: The GAW20 group formed on the theme of methods for association analyses of repeated measures comprised 4sets of investigators. The provided “real” data set included genotypes obtained from a human whole-genome association study based on longitudinal measurements of triglycerides (TGs) and high-density lipoprotein in addition to methylation levels before and after administration of fenofibrate. The simulated data set contained 200 replications of methylation levels and posttreatment TGs, mimicking the real data set.

Results: The different investigators in the group focused on the statistical challenges unique to family-based association analyses of phenotypes measured longitudinally and applied a wide spectrum of …

How Behavior Of Nontarget Species Affects Perceived Accuracy Of Scat Detection Dog Surveys, Karen E. Dematteo, Linsey W. Blake, Julie K. Young, Barbara Davenport

Wildland Resources Faculty Publications

Detection dogs, specially trained domestic dogs (Canis familiaris), have become a valuable, noninvasive, conservation tool because they remove the dependence of attracting species to a particular location. Further, detection dogs locate samples independent of appearance, composition, or visibility allowing researchers to collect large sets of unbiased samples that can be used in complex ecological queries. One question not fully addressed is why samples from nontarget species are inadvertently collected during detection dog surveys. While a common explanation has been incomplete handler or dog training, our study aimed to explore alternative explanations. Our trials demonstrate that a scat’s genetic …

Dobi Studies, Teaches The Marvels Of Genetics, Aldemaro Romero Jr.

Publications and Research

“When I was in third grade, a parent of one of the other students brought a number of cats to the library on a Saturday and talked about how there are all these different hereditary patterns that contribute to their coat colors and appearance, like spots, stripes, and white paws. I was just hooked because I loved cats, and I said this is what I want to do.”

That’s how Dr. Krista Dobi explains why she became a geneticist. A native of North Brunswick, New Jersey, Dobi received a bachelor of arts from Princeton University and a doctorate in genetics …

Dietary Docosahexaenoic Acid Prevents Silica-Induced Development Of Pulmonary Ectopic Germinal Centers And Glomerulonephritis In The Lupus-Prone Nzbwf1 Mouse, Melissa A. Bates, Peyman Akbari, Kristen N. Gilley, James G. Wagner, Ning Li, Anna K. Kopec, Kathryn A. Wierenga, Daven Jackson-Humbles, Christina Brandenberger, Andrij Holian, Abby D. Benninghoff, Jack R. Harkema, James J. Pestka

Animal, Dairy, and Veterinary Science Faculty Publications

Ectopic lymphoid structures (ELS) consist of B-cell and T-cell aggregates that are initiated de novo in inflamed tissues outside of secondary lymphoid organs. When organized within follicular dendritic cell (FDC) networks, ELS contain functional germinal centers that can yield autoantibody-secreting plasma cells and promote autoimmune disease. Intranasal instillation of lupus-prone mice with crystalline silica (cSiO₂), a respirable particle linked to human lupus, triggers ELS formation in the lung, systemic autoantibodies, and early onset of glomerulonephritis. Here we tested the hypothesis that consumption of docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid with anti-inflammatory properties, influences the temporal profile …

Susceptibility Genes To Plant Viruses, Hernan Garcia-Ruiz

Nebraska Center for Virology: Faculty Publications

Plant viruses use cellular factors and resources to replicate and move. Plants respond to viral infection by several mechanisms, including innate immunity, autophagy, and gene silencing, that viruses must evade or suppress. Thus, the establishment of infection is genetically determined by the availability of host factors necessary for virus replication and movement and by the balance between plant defense and viral suppression of defense responses. Host factors may have antiviral or proviral activities. Proviral factors condition susceptibility to viruses by participating in processes essential to the virus. Here, we review current advances in the identification and characterization of host factors …

Identification And Characterization Of Nitrogen Fixing Bacteria Associated With Kudzu Root Nodules, Chasity Lawless, Michelle Zedonek, Debbie Curtis, Jonda Scharringhausen, Jared Bryant, Wendy A. Dustman, Alexandra M. Kurtz, Bekah Ward Dr.

Georgia Journal of Science

Pueraria montana, better known as kudzu, is an invasive species rapidly spreading throughout the southeastern United States. This plant can form root nodules which house nitrogen-fixing bacteria, allowing atmospheric nitrogen to be converted into biologically available forms of nitrogen for use by the plant host. Given the centrality of these bacteria to the spread of kudzu, isolates from nodules were characterized after collection from seven different locations across the metropolitan Atlanta area. Twenty-five isolates were grown on two different variants of nitrogen free media. Four different carbon sources were evaluated as well. Finally, growth under both aerobic and anaerobic …

Genetic Determinants Of Telomere Length In African American Youth, Andrew M. Zeiger, Marquitta J. White, Celeste Eng, Sam S. Oh, Jonathan Witonsky, Pagé C. Goddard, Maria G. Contreras, Jennifer R. Elhawary, Donglei Hu, Angel C. Y. Mak, Eunice Y. Lee, Kevin L. Keys, Lesly-Anne Samedy, Oona Risse Adams, Joaquín Magaña, Scott Huntsman, Sandra Salazar, Adam Davis, Kelley Meade, Emerita Brigino-Buenaventura, Michael A. Lenoir, Harold J. Farber, Kirsten Bibbins-Domingo, Luisa N. Borrell, Esteban G. Burchard

Publications and Research

Telomere length (TL) is associated with numerous disease states and is affected by genetic and environmental factors. However, TL has been mostly studied in adult populations of European or Asian ancestry. These studies have identified 34 TL-associated genetic variants recently used as genetic proxies for TL. The generalizability of these associations to pediatric populations and racially diverse populations, specifically of African ancestry, remains unclear. Furthermore, six novel variants associated with TL in a population of European children have been identified but not validated. We measured TL from whole blood samples of 492 healthy African American youth (children and adolescents between …

Histone Deacetylase Inhibitors Prevent Persistent Hypersensitivity In An Orofacial Neuropathic Pain Model, Robert J. Danaher, Liping Zhang, Connor J. Donley, Nashwin A. Laungani, S. Elise Hui, Craig S. Miller, Karin N. Westlund

Oral Health Practice Faculty Publications

Chronic orofacial pain is a significant health problem requiring identification of regulating processes. Involvement of epigenetic modifications that is reported for hindlimb neuropathic pain experimental models, however, is less well studied in cranial nerve pain models. Three independent observations reported here are the (1) epigenetic profile in mouse trigeminal ganglia (TG) after trigeminal inflammatory compression (TIC) nerve injury mouse model determined by gene expression microarray, (2) H3K9 acetylation pattern in TG by immunohistochemistry, and (3) efficacy of histone deacetylase (HDAC) inhibitors to attenuate development of hypersensitivity. After TIC injury, ipsilateral whisker pad mechanical sensitization develops by day 3 and persists …

Surface Immobilization Of Redox-Labile Fluorescent Probes: Enabling Single-Cell Co-Profiling Of Aerobic Glycolysis And Oncogenic Protein Signaling Activities., Zhonghan Li, Hanjun Cheng, Shiqun Shao, Xiang Lu, Li Mo, Jonathan Tsang, Pu Zeng, Zhili Guo, Siwen Wang, David A Nathanson, James R Heath, Wei Wei, Min Xue

Articles, Abstracts, and Reports

An analytical method is described for profiling lactate production in single cells via the use of coupled enzyme reactions on surface-grafted resazurin molecules. The immobilization of the redox-labile probes was achieved through chemical modifications on resazurin, followed by bio-orthogonal click reactions. The lactate detection was demonstrated to be sensitive and specific. The method was incorporated into a single-cell barcode chip for simultaneous quantification of aerobic glycolysis activities and oncogenic signaling phosphoproteins in cancer. The interplay between glycolysis and oncogenic signaling activities was interrogated on a glioblastoma cell line. Results revealed a drug-induced oncogenic signaling reliance accompanying shifted metabolic paradigms. A …

The Combinatorics Of The Foldings Of Rna, Katrina Teunis

Student Summer Scholars Manuscripts

RNA, much like DNA, is made up of four building blocks called nucleotides, Adenine, Guanine, Cytosine, and Uracil. These nucleotides form words that like to fold in on itself and bond together, each type of nucleotide bonding with only one other type of nucleotide. Therefore, order and number of nucleotides present will determine how many times the strand of RNA can fold. Using these guidelines, we considered what happens when we have only one bonding pair. Expanding on what was proven in "k-Foldability of Words” (2017), we were able to expand on the number of ways a word can fold …

Underlying Contribution Of Executive Functioning To Cognition And Academic Achievement In Individuals With Dystrophinopathy, Robert Fee

Dissertations, Theses, and Capstone Projects

Dystrophinopathy is a genetic disorder that results in the lack of or abnormal expression of the protein dystrophin. It is a disorder that alters cell structure and function, impacts the developing brain and brain function, presents with multi-domain cognitive deficits, and influences both mood and behavior. Cognitive impairments appear to be more localized to specific areas of functioning rather than a global deficit; however, deficits have been identified across multiple cognitive domains including language and aspects of executive functioning. A careful examination of the cognitive phenotype and its association to mutations affecting CNS isoforms is necessary to clarify the neuropsychological …

Hypermethylation Of Mir21 In Cd4+ T Cells From Patients With Relapsing-Remitting Multiple Sclerosis Associates With Lower Mirna-21 Levels And Concomitant Up-Regulation Of Its Target Genes, Sabrina Ruhrmann, Ewoud Ewing, Eliane Piket, Lara Kular, Julio Cesar Cetrulo Lorenzi, Sunjay Jude Fernandes, Hiromasa Morikawa, Shahin Aeinehband, Sergi Sayols-Baixeras, Stella Aslibekyan, Devin M. Absher, Donna K. Arnett, Jesper Tegner, David Gomez-Cabrero, Fredrik Piehl, Maja Jagodic

Epidemiology and Environmental Health Faculty Publications

Background: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system caused by genetic and environmental factors. DNA methylation, an epigenetic mechanism that controls genome activity, may provide a link between genetic and environmental risk factors.

Objective: We sought to identify DNA methylation changes in CD4+ T cells in patients with relapsing-remitting (RR-MS) and secondary-progressive (SP-MS) disease and healthy controls (HC).

Methods: We performed DNA methylation analysis in CD4+ T cells from RR-MS, SP-MS, and HC and associated identified changes with the nearby risk allele, smoking, age, and gene expression.

Results: We observed significant methylation differences in …

Red Fox Genome Assembly Identifies Genomic Regions Associated With Tame And Aggressive Behaviours, Anna V. Kukekova, Jennifer L. Johnson, Xueyan Xiang, Shaohong Feng, Shiping Liu, Halie M. Rando, Anastasiya V. Kharlamova, Yury Herbeck, Natalya A. Serdyukova, Zijun Xiong, Violetta Beklemischeva, Klaus Peter Koepfli, Rimma G. Gulevich, Anastasiya V. Vladimirova, Jessica P. Hekman, Polina L. Perelman, Aleksander S. Graphodatsky, Stephen J. O’Brien, Xu Wang, Andrew G. Clark, Gregory M. Acland, Lyudmila N. Trut, Guojie Zhang

Biology Faculty Articles

Strains of red fox (Vulpes vulpes) with markedly different behavioural phenotypes have been developed in the famous long-term selective breeding programme known as the Russian farm-fox experiment. Here we sequenced and assembled the red fox genome and re-sequenced a subset of foxes from the tame, aggressive and conventional farm-bred populations to identify genomic regions associated with the response to selection for behaviour. Analysis of the re-sequenced genomes identified 103 regions with either significantly decreased heterozygosity in one of the three populations or increased divergence between the populations. A strong positional candidate gene for tame behaviour was highlighted: SorCS1, which encodes …

Integration Of Bmp And Insulin/Igf-1 Signaling Regulates Multiple Homeostatic Functions In Caenorhabditis Elegans, James F. Clark

Dissertations, Theses, and Capstone Projects

The maintenance of homeostatic functions is key to the survival and well-being of an organism. Regulation of homeostasis relies on varied inputs, both intrinsic and extrinsic, to potentiate a web of interconnected signaling relays. Insulin/IGF-1 signaling (IIS) is a well-known regulator of glucose and lipid metabolism, as well as having far reaching effects in other homeostatic mechanisms. On the other hand, bone morphogenetic protein (BMP), a member of the transforming growth factor beta signaling superfamily, is known for its role in differentiation and development, with only recent studies highlighting potential roles in metabolic homeostasis. Here we elucidate new functions for …

Confirming World-Wide Distribution Of An Agriculturally Important Lacewing, Chrysoperla Zastrowi Sillemi, Using Songs, Morphology, Mitochondrial Gene Sequencing, And Phylogenetic Reconstruction, Zoe Mandese

Honors Scholar Theses

The Chrysoperla carnea-group of green lacewings is a cryptic species complex. Species within the group are morphologically similar, yet isolated from one another via reproductive mating song. Chrysoperla zastrowi, a species within the carnea-group, is currently described with a distribution ranging from South Africa to the Middle East and India. However, recent collections of carnea-group lacewings from Guatemala and California were preliminarily identified as Chrysoperla zastrowi based upon similarities in their vibrational courtship songs. This analysis aims to place six specimens, collected by collaborators in Guatemala, Armenia, Iran, and California, into a pre-existing phylogeny of the …

Aspen Recruitment In The Yellowstone Region Linked To Reduced Herbivory After Large Carnivore Restoration, Luke E. Painter, Robert L. Beschta, Eric J. Larsen, William J. Ripple

Aspen Bibliography

Quaking aspen (Populus tremuloides) recruitment during the 1980s–90s was suppressed by Rocky Mountain elk (Cervus canadensis) herbivory on winter ranges in the Yellowstone region, and saplings (young aspen taller than 2 m) were rare. Following the 1995–96 reintroduction of gray wolves (Canis lupus), browsing decreased and sapling recruitment increased in Yellowstone National Park. We compared aspen data from inside the park to data collected in three winter ranges outside the park. For most areas, the percentage of young aspen browsed annually was 80–100% in 1997–98, decreasing to 30–60% in 2011–15. Sapling recruitment was inversely …

Effects Of Stand Structure, Browsing, And Biophysical Conditions On Regeneration Following Mountain Pine Beetle In Mixed Lodgepole Pine And Aspen Forests Of The Southern Rockies, Kristen A. Pelz, Frederick W. Smith

Aspen Bibliography

Aspen (Populus tremuloides) and lodgepole pine (Pinus contorta var. latifolia) co-occur in the southern Rocky Mountains (USA), where mountain pine beetle (MPB, Dendroctonus ponderosae) has caused extensive lodgepole pine mortality since the late 1990s. Both species excel in post-disturbance high-light environments, but lodgepole pine has generally been thought to establish poorly on undisturbed seedbeds, and aspen suckering may be inhibited by intact aspen overstory. We ask whether lodgepole pine and aspen will regenerate in sufficient quantities to revegetate these forests. We visited a random sample of aspen and lodgepole pine stands across the affected landscape …

Transcriptomic Insights On The Virulence-Controlling Csra, Badr, Rpon, And Rpos Regulatory Networks In The Lyme Disease Spirochete, William K. Arnold, Christina R. Savage, Kathryn G. Lethbridge, Trever C. Smith, Catherine A. Brisette, Janakiram Seshu, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Borrelia burgdorferi, the causative agent of Lyme disease, survives in nature through a cycle that alternates between ticks and vertebrates. To facilitate this defined lifestyle, B. burgdorferi has evolved a gene regulatory network that ensures transmission between those hosts, along with specific adaptations to niches within each host. Several regulatory proteins are known to be essential for the bacterium to complete these critical tasks, but interactions between regulators had not previously been investigated in detail, due to experimental uses of different strain backgrounds and growth conditions. To address that deficit in knowledge, the transcriptomic impacts of four critical …

Characterization Of Mrna Polyadenylation In The Apicomplexa, Ashley T. Stevens, Daniel K. Howe, Arthur G. Hunt

Plant and Soil Sciences Faculty Publications

Messenger RNA polyadenylation is a universal aspect of gene expression in eukaryotes. In well-established model organisms, this process is mediated by a conserved complex of 15–20 subunits. To better understand this process in apicomplexans, a group of unicellular parasites that causes serious disease in humans and livestock, a computational and high throughput sequencing study of the polyadenylation complex and poly(A) sites in several species was conducted. BLAST-based searches for orthologs of the human polyadenylation complex yielded clear matches to only two—poly(A) polymerase and CPSF73—of the 19 proteins used as queries in this analysis. As the human subunits that recognize the …

Gain-Of-Function Experiments With Bacteriophage Lambda Uncover Residues Under Diversifying Selection In Nature, Rohan Maddamsetti, Daniel T. Johnson, Stephanie J. Spielman, Katherine L. Petrie, Debora S. Marks, Justin R. Meyer

College of Science & Mathematics Departmental Research

Viral gain‐of‐function mutations frequently evolve during laboratory experiments. Whether the specific mutations that evolve in the lab also evolve in nature and whether they have the same impact on evolution in the real world is unknown. We studied a model virus, bacteriophage λ, that repeatedly evolves to exploit a new host receptor under typical laboratory conditions. Here, we demonstrate that two residues of λ’s J protein are required for the new function. In natural λ variants, these amino acid sites are highly diverse and evolve at high rates. Insertions and deletions at these locations are associated with phylogenetic patterns indicative …

Regulated Capture Of Vκ Gene Topologically Associating Domains By Transcription Factories, Sophiya Karki, Domenick E. Kennedy, Kaitlin Mclean, Adrian T. Grzybowski, Mark Maienschein-Cline, Shiladitya Banerjee, Heping Xu, Elizabeth Davis, Malay Mandal, Christine Labno, Sarah E. Powers, Michelle M. Le Beau, Aaron R. Dinner, Harinder Singh, Alexander J. Ruthenburg, Marcus R. Clark

Biology Department Faculty Articles

Expression of vast repertoires of antigen receptors by lymphocytes, with each cell expressing a single receptor, requires stochastic activation of individual variable (V) genes for transcription and recombination. How this occurs remains unknown. Using single-cell RNA sequencing (scRNA-seq) and allelic variation, we show that individual pre-B cells monoallelically transcribe divergent arrays of Vκ genes, thereby opening stochastic repertoires for subsequent Vκ-Jκ recombination. Transcription occurs upon translocation of Vκ genes to RNA polymerase II arrayed on the nuclear matrix in transcription factories. Transcription is anchored by CTCF-bound sites or E2A-loaded Vκ promotors and continues over large genomic distances delimited only by …

Genome-Wide Association Study For Variants That Modulate Relationships Between Cerebrospinal Fluid Amyloid-Beta 42, Tau, And P-Tau Levels, Taylor J. Maxwell, Chris Corcoran, Jorge L. Del-Aguila, John P. Budde, Yuetiva Deming, Carlos Cruchaga, Alison M. Goate, John S. K. Kauwe, Alzheimer's Disease Neuroimaging Initiative

Mathematics and Statistics Faculty Publications

Background: A relationship quantitative trait locus exists when the correlation between multiple traits varies by genotype for that locus. Relationship quantitative trait loci (rQTL) are often involved in gene-by-gene (G×G) interactions or gene-by-environmental interactions, making them a powerful tool for detecting G×G.

Methods: We performed genome-wide association studies to identify rQTL between tau and Aβ42 and ptau and Aβ42 with over 3000 individuals using age, gender, series, APOE ε2, APOE ε4, and two principal components for population structure as covariates. Each significant rQTL was separately screened for interactions with other loci for each trait in the rQTL model. Parametric bootstrapping …

Ubiquitin Regulation: The Histone Modifying Enzyme's Story, Jianlin Wang, Zhaoping Qiu, Yadi Wu

Pharmacology and Nutritional Sciences Faculty Publications

Histone post-translational modifications influence many fundamental cellular events by regulating chromatin structure and gene transcriptional activity. These modifications are highly dynamic and tightly controlled, with many enzymes devoted to the addition and removal of these modifications. Interestingly, these modifying enzymes are themselves fine-tuned and precisely regulated at the level of protein turnover by ubiquitin-proteasomal processing. Here, we focus on recent progress centered on the mechanisms regulating ubiquitination of histone modifying enzymes, including ubiquitin proteasomal degradation and the reverse process of deubiquitination. We will also discuss the potential pathophysiological significance of these processes.

Mobile Elements Shape Plastome Evolution In Ferns, Tanner A. Robison, Amanda L. Grusz, Paul G. Wolf, Jeffrey P. Mower, Blake D. Fauskee, Karla Sosa, Eric Schuettpelz

Biology Faculty Publications

Plastid genomes display remarkable organizational stability over evolutionary time. From green algae to angiosperms, most plastid genomes are largely collinear, with only a few cases of inversion, gene loss, or, in extremely rare cases, gene addition. These plastome insertions are mostly clade-specific and are typically of nuclear or mitochondrial origin. Here, we expand on these findings and present the first family-level survey of plastome evolution in ferns, revealing a novel suite of dynamic mobile elements. Comparative plastome analyses of the Pteridaceae expose several mobile open reading frames that vary in sequence length, insertion site, and configuration among sampled taxa. Even …

Open-Source Tools For Dense Facial Tissue Depth Mapping (Ftdm) Of Computed Tomography Models, Terrie Simmons-Ehrhardt, Catyana Falsetti, Anthony B. Falsetti, Christopher J. Ehrhardt

Human Biology Open Access Pre-Prints

Computed tomography (CT) scans provide anthropologists with a resource to generate three- dimensional (3D) digital skeletal material to expand quantification methods and build more standardized reference collections. The ability to visualize and manipulate the bone and skin of the face simultaneously in a 3D digital environment introduces a new way for forensic facial approximation practitioners to access and study the face. Craniofacial relationships can be quantified with landmarks or with surface processing software that can quantify the geometric properties of the entire 3D facial surface. This paper describes tools for the generation of dense facial tissue depth maps (FTDMs) using …

Of Typicality And Predictive Distributions In Discriminant Function Analysis, Lyle W. Konigsberg, Susan R. Frankenberg

Human Biology Open Access Pre-Prints

While discriminant function analysis is an inherently Bayesian method, researchers attempting to estimate ancestry in human skeletal samples often follow discriminant function analysis with the calculation of frequentist-based typicalities for assigning group membership. Such an approach is problematic in that it fails to account for admixture and for variation in why individuals may be classified as outliers, or non-members of particular groups. This paper presents an argument and methodology for employing a fully Bayesian approach in discriminant function analysis applied to cases of ancestry estimation. The approach requires adding the calculation, or estimation, of predictive distributions as the final step …

Transcriptional Response Of Honey Bee (Apis Mellifera) To Differential Nutritional Status And Nosema Infection, Farida Azzouz-Olden, Arthur G. Hunt, Gloria Degrandi-Hoffman

Plant and Soil Sciences Faculty Publications

Background: Bees are confronting several environmental challenges, including the intermingled effects of malnutrition and disease. Intuitively, pollen is the healthiest nutritional choice, however, commercial substitutes, such as Bee-Pro and MegaBee, are widely used. Herein we examined how feeding natural and artificial diets shapes transcription in the abdomen of the honey bee, and how transcription shifts in combination with Nosema parasitism.

Results: Gene ontology enrichment revealed that, compared with poor diet (carbohydrates [C]), bees fed pollen (P > C), Bee-Pro (B > C), and MegaBee (M > C) showed a broad upregulation of metabolic processes, especially lipids; however, pollen feeding promoted more functions, and …

N-Terminal Domain Of Human Uracil Dna Glycosylase (Hung2) Promotes Targeting To Uracil Sites Adjacent To Ssdna-Dsdna Junctions, Brian P Weiser, Gaddiel Rodriguez, Philip A Cole, James T Stivers

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The N-terminal domain (NTD) of nuclear human uracil DNA glycosylase (hUNG2) assists in targeting hUNG2 to replication forks through specific interactions with replication protein A (RPA). Here, we explored hUNG2 activity in the presence and absence of RPA using substrates with ssDNA-dsDNA junctions that mimic structural features of the replication fork and transcriptional R-loops. We find that when RPA is tightly bound to the ssDNA overhang of junction DNA substrates, base excision by hUNG2 is strongly biased toward uracils located 21 bp or less from the ssDNA-dsDNA junction. In the absence of RPA, hUNG2 still showed an 8-fold excision bias …

Double-Stranded Rna Binding Protein, Staufen, Is Required For The Initiation Of Rnai In Coleopteran Insects, June-Sun Yoon, Kanakachari Mogilicherla, Dhandapani Gurusamy, Xien Chen, Shankar C. R. R. Chereddy, Subba R. Palli

Entomology Faculty Publications

RNA interference (RNAi) is being used to develop methods to control pests and disease vectors. RNAi is robust and systemic in coleopteran insects but is quite variable in other insects. The determinants of efficient RNAi in coleopterans, as well as its potential mechanisms of resistance, are not known. RNAi screen identified a double-stranded RNA binding protein (StaufenC) as a major player in RNAi. StaufenC homologs have been identified in only coleopteran insects. Experiments in two coleopteran insects, Leptinotarsa decemlineata and Tribolium castaneum, showed the requirement of StaufenC for RNAi, especially for processing of double-stranded RNA (dsRNA) to small interfering …