Biochemistry, Biophysics, and Structural Biology Commons^™

Bone Morphogenetic Protein Signaling Requirement In Centripetal Migration In Drosophila Melanogaster Oogenesis, Sheila Mosallaei

UNLV Theses, Dissertations, Professional Papers, and Capstones

Cells interact with each other via signals to coordinate migration for proper tissue development and maintenance, immunity and tissue repair. Signals regulate migration via changes to cytoskeletal components or transcriptional regulation. Here, I used Drosophila melanogaster to investigate whether and how a transcriptional signal, Bone Morphogenetic Protein signaling, drives a cell migration, centripetal migration. The migrating cells, centripetal follicle cells, consist of two subsets of cells, “leading” and “following” centripetal follicle cells, that although adjacent to each other, migrate differently. The differences in modes of migration correlate to differential gene expression in the centripetal follicle cells. The leading centripetal follicle …

Functional Coordination Of Bet Family Proteins Underlies Altered Transcription Associated With Memory Impairment In Fragile X Syndrome, Seung Kyoon Kim, Xihui Liu, Jongmin Park, Dahun Um, Gokhul Kilaru, Cheng Ming Chiang, Mingon Kang, Kimberly M. Huber, Keunsoo Kang, Tae Kyung Kim

Computer Science Faculty Research

Bromodomain and extraterminal proteins (BET) are epigenetic readers that play critical roles in gene regulation. Pharmacologic inhibition of the bromodomain present in all BET family members is a promising therapeutic strategy for various diseases, but its impact on individual family members has not been well understood. Using a transcriptional induction paradigm in neurons, we have systematically demonstrated that three major BET family proteins (BRD2/3/4) participated in transcription with different recruitment kinetics, interdependency, and sensitivity to a bromodomain inhibitor, JQ1. In a mouse model of fragile X syndrome (FXS), BRD2/3 and BRD4 showed oppositely altered expression and chromatin binding, correlating with …

Regulation Of Dna Replication Licensing And Re-Replication By Cdt1, Hui Zhang

Chemistry and Biochemistry Faculty Research

In eukaryotic cells, DNA replication licensing is precisely regulated to ensure that the initiation of genomic DNA replication in S phase occurs once and only once for each mitotic cell division. A key regulatory mechanism by which DNA re-replication is suppressed is the S phase-dependent proteolysis of Cdt1, an essential replication protein for licensing DNA replication origins by loading the Mcm2-7 replication helicase for DNA duplication in S phase. Cdt1 degradation is mediated by CRL4 ubiquitin E3 ligase, which further requires Cdt1 binding to proliferating cell nuclear antigen (PCNA) through a PIP box domain in Cdt1 during DNA synthesis. Recent …

The Role Of Nutrition And Hormone Signaling In Extended Larval Development And Obesity In Starvation-Selected Drosophila Melanogaster, Jennifer M. Clark

UNLV Theses, Dissertations, Professional Papers, and Capstones

Brief periods of starvation are a common stressor that most animals encounter in the wild and must be able to survive in order to maximize their fitness. Starvation resistance of the adult fruit fly, Drosophila melanogaster, is thought to be primarily conferred by adult fat stores, body size, metabolic rate, behavior, and activity levels. Additionally, flies selected for starvation resistance also often show delayed pupariation, which is usually indicative of altered hormone signaling. How starvation selection extends development and if it contributes to adult starvation resistance remains incompletely studied. Identifying the targets of starvation selection that cause extended development and …

Understanding The Role Of Ano1 In Oral Cancer, Mallary Forrest

UNLV Theses, Dissertations, Professional Papers, and Capstones

In 2008, the gene ANO1 was discovered to encode a calcium activated chloride channel. This gene is located on the 11q13 locus, a locus that is commonly amplified in many cancers including cancer of the head and neck. ANO1 is situated in close proximity to genes associated with growth and apoptosis. As rapid proliferation and lack of apoptosis are hallmark characteristics of cancer, growth factors and apoptosis mediators are expected to be altered in cancer. But what does a calcium activated chloride channel have to contribute to cancer’s pathogenesis? Is it an active gene in cancer progression or is it …

Effects Of Curcumin And Its Different Formulations In Preclinical And Clinical Studies Of Peripheral Neuropathic And Postoperative Pain: A Comprehensive Review, Paramita Basu, Camelia Maier, Arpita Basu

Kinesiology and Nutrition Sciences Faculty Research

Lesion or disease of the somatosensory system leads to the development of neuropathic pain. Peripheral neuropathic pain encompasses damage or injury of the peripheral nervous system. On the other hand, 10–15% of individuals suffer from acute postoperative pain followed by persistent pain after undergoing surgeries. Antidepressants, anticonvulsants, baclofen, and clonidine are used to treat peripheral neuropathy, whereas opioids are used to treat postoperative pain. The negative effects associated with these drugs emphasize the search for alternative therapeutics with better efficacy and fewer side effects. Curcumin, a polyphenol isolated from the roots of Curcuma longa, possesses antibacterial, antioxidant, and anti-inflammatory properties. …

Vitamin D3 Induces Mesenchymal-To-Endothelial Transition And Promotes A Proangiogenic Niche Through Igf-1 Signaling, Lei Chen, Anweshan Samanta, Lin Zhao, Nathaniel R. Dudley, Tanner Buehler, Robert J. Vincent, Jeryl Hauptman, Magdy Girgis, Buddhadeb Dawn

School of Medicine Faculty Research

Biological Sciences; Physiology; Molecular Biology; Cell Biology

Rasagiline Effects On Glucose Metabolism, Cognition, And Tau In Alzheimer’S Dementia, Dawn C. Matthews, Aaron Ritter, Ronald G. Thomas, Randolph D. Andrews, Ana S. Lukic, Carolyn Revta, Jefferson W. Kinney, Babak Tousi, James B. Leverenz, Howard Fillit, Kate Zhong, Howard H. Feldman, Jeffrey Cummings

Integrated Health Sciences Faculty Research

Background: A Phase II proof of concept (POC) randomized clinical trial was conducted to evaluate the effects of rasagiline, a monoamine oxidase B (MAO-B) inhibitor approved for Parkinson disease, in mild to moderate Alzheimer's disease (AD). The primary objective was to determine if 1 mg of rasagiline daily for 24 weeks is associated with improved regional brain metabolism (fluorodeoxyglucose–positron emission tomography [FDG-PET]) compared to placebo. Secondary objectives included measurement of effects on tau PET and evaluation of directional consistency of clinical end points. Methods: This was a double-blind, parallel group, placebo-controlled, community-based, three-site trial of 50 participants randomized 1:1 to …

Ubiquitin Ligation To F-Box Protein Targets By Scf–Rbr E3–E3 Super-Assembly, Daniel Horn-Ghetko, David T. Krist, J. Rajan Prabu, Kheewoong Baek, Monique P.C. Mulder, Maren Klügel, Daniel C. Scott, Huib Ovaa, Gary Kleiger, Brenda A. Schulman

Chemistry and Biochemistry Faculty Research

© 2021, The Author(s). E3 ligases are typically classified by hallmark domains such as RING and RBR, which are thought to specify unique catalytic mechanisms of ubiquitin transfer to recruited substrates1,2. However, rather than functioning individually, many neddylated cullin–RING E3 ligases (CRLs) and RBR-type E3 ligases in the ARIH family—which together account for nearly half of all ubiquitin ligases in humans—form E3–E3 super-assemblies3–7. Here, by studying CRLs in the SKP1–CUL1–F-box (SCF) family, we show how neddylated SCF ligases and ARIH1 (an RBR-type E3 ligase) co-evolved to ubiquitylate diverse substrates presented on various F-box proteins. We developed activity-based chemical probes that …

Transcriptional Coupling And Repair Of 8-Oxog Activate A Reca-Dependent Checkpoint That Controls The Onset Of Sporulation In Bacillus Subtilis, Valeria P. Suárez, Lissett E. Martínez, Hilda C. Leyva-Sánchez, Luz I. Valenzuela-García, Reyna Lara-Martínez, Luis F. Jiménez-García, Norma Ramírez-Ramírez, Armando Obregon-Herrera, Mayra Cuéllar-Cruz, Eduardo A. Robleto, Mario Pedraza-Reyes

Life Sciences Faculty Research

© 2021, The Author(s). During sporulation Bacillus subtilis Mfd couples transcription to nucleotide excision repair (NER) to eliminate DNA distorting lesions. Here, we report a significant decline in sporulation following Mfd disruption, which was manifested in the absence of external DNA-damage suggesting that spontaneous lesions activate the function of Mfd for an efficient sporogenesis. Accordingly, a dramatic decline in sporulation efficiency took place in a B. subtilis strain lacking Mfd and the repair/prevention guanine oxidized (GO) system (hereafter, the ∆GO system), composed by YtkD, MutM and MutY. Furthermore, the simultaneous absence of Mfd and the GO system, (i) sensitized sporulating …

Impact Of Uv-Induced Ozone And Low-Energy Ar+-Ion Cleaning On The Chemical Structure Of Cu(In,Ga)(S,Se)2 Absorber Surfaces, Victor R. Van Maris, Dirk Hauschild, Thomas P. Niesen, Patrick Eraerds, Thomas Dalibor, Jörg Palm, Monika Blum, Wanli Yang, Clemens Heske, Lothar Weinhardt

Chemistry and Biochemistry Faculty Research

Dry buffer layer deposition techniques for chalcopyrite (CIGSSe)-based thin-film solar cells lack the surface-cleaning characteristics of the commonly used CdS or Zn(O,S) wet-chemical bath deposition. A UV-induced ozone and/or a low-energy Ar+-ion treatment could provide dry CIGSSe surface cleaning steps. To study the impact of these treatments, the chemical surface structure of a CIGSSe absorber is investigated. For this purpose, a set of surface-sensitive spectroscopic methods, i.e., laboratory-based x-ray photoelectron spectroscopy and x-ray-excited Auger electron spectroscopy, is combined with synchrotron-based soft x-ray emission spectroscopy. After treatment times as short as 15 s, the UV-induced ozone treatment decreases the amount of …

Using Novel Mouse Knockout Models To Study The Roles Of Asm (Acid Sphingomyelinase) In The Regulation Of Multiple Stem Cell Compartments In Vivo, Amro Abdalla

UNLV Theses, Dissertations, Professional Papers, and Capstones

Acid Sphingomyelinase (ASM) is a lipid-modifying enzyme that breaks down sphingomyelin lipids into ceramide and phosphorylcholine. Genetic mutations in the human ASM gene leads to Niemann pick diseases (NPD) type A & B. In NPD type A, patients die between 1-2 years old due to severe neurological complications, while NPD type B patients live to adulthood but suffer from severe visceral organ complications. Type A is usually associated with complete inactivation of the ASM gene. The hallmark of NPD is Purkinje neuron (PN) death. PNs, the major neurons in the cerebellum part of the brain, regulate the balance and fine …

Transcriptional Control Of Virulence Genes In The Bacterial Pathogen Shigella Flexneri, Joy Asami Mckenna

UNLV Theses, Dissertations, Professional Papers, and Capstones

Shigella species, the causal agents of bacillary dysentery, use a type III secretion system (T3SS) to inject two waves of virulence proteins, known as effectors, into the human colonic epithelium to subvert host cell machinery. Transcriptional regulation of these virulence genes is controlled by the three-tiered VirF/VirB/MxiE signaling cascade. Of these, VirB has the largest regulon (~50 genes); however, VirB regulatory properties are poorly understood. To date, VirB is known to function to counter or 'anti-silence' transcriptional silencing mediated by the histone-like nucleoid structuring protein H-NS. To better understand VirB regulation, my colleagues and I chose to better define the …

In Vivo Biosynthesis Of Inorganic Nanomaterials Using Eukaryotes - A Review, Ashiqur Rahman, Julia Lin, Francisco E. Jaramillo, Dennis A. Bazylinski, Clayton Jeffryes, Si Amar Dahoumane

Life Sciences Faculty Research

Bionanotechnology, the use of biological resources to produce novel, valuable nanomaterials, has witnessed tremendous developments over the past two decades. This eco-friendly and sustainable approach enables the synthesis of numerous, diverse types of useful nanomaterials for many medical, commercial, and scientific applications. Countless reviews describing the biosynthesis of nanomaterials have been published. However, to the best of our knowledge, no review has been exclusively focused on the in vivo biosynthesis of inorganic nanomaterials. Therefore, the present review is dedicated to filling this gap by describing the many different facets of the in vivo biosynthesis of nanoparticles (NPs) using living eukaryotic …

Stereotactic Radiosurgery Implementation At Utah Valley Hospital, Ryan Sharp

UNLV Theses, Dissertations, Professional Papers, and Capstones

Utah Valley Hospital (UVH) implemented a stereotactic radiosurgery (SRS) program as an additional line of service. SRS as defined by the American College of Radiology is radiation therapy delivered via stereotactic guidance with approximately 1 mm targeting accuracy to intracranial targets in 1-5 fractions. Effectively implementing the SRS program at UVH requires the adoption and implementation of hardware and software technologies, a review of the clinical workflow with appropriate quality assurance tests, and the assessment of additional technologies that will further enhance the capabilities of the program. The scope of this work is to include a comprehensive writeup of the …

Investigating The Mechanisms Responsible For Cephalosporin Resistance In Clostridioides Difficile Strain 630, Lara Anna Turello

UNLV Theses, Dissertations, Professional Papers, and Capstones

Clostridioides difficile infection (CDI) is one of the most common nosocomial infections worldwide. A major risk factor for CDI is antibiotic therapy, due to C. difficile’s resistance to a myriad of antibiotics—one of which are cephalosporins. Cephalosporins are ß-lactam antibiotics that function by binding to the active site of penicillin-binding proteins (PBPs), thus inhibiting peptidoglycan synthesis and leading to cell lysis. Gram-positive bacteria can counteract ß-lactams by (i) producing ß-lactamases, (ii) expressing modified PBPs, or (iii) by expressing efflux pumps.

Genomic analysis of C. difficile strain 630 revealed the presence of at least 31 putative ß-lactam resistance genes that encode …

Utilizing Breathing Techniques To Maximize Training Performance, Peyton Cater

UNLV Theses, Dissertations, Professional Papers, and Capstones

Anaerobic exercise causes metabolic acidosis to occur in the muscle, which is unfavorable for sustaining high intensity activity, as fatigue starts to set in. In order to compensate for the onset of fatigue produced by an acidic environment, respiratory alkalosis, induced by hyperventilation, can be performed to mitigate these effects. In contrast, research has shown that slowing down the breath rate, such as a two second inhale and three second exhale, has led to an increase in performance outcomes. Purpose: To investigate power output and the physiological responses after implementation of different breathing techniques during the recovery periods of intermittent …

Rapid Evolution Of Starvation Resistance In Drosophila: Physiological And Molecular Mechanisms, Austin Joseph Mckenna

UNLV Theses, Dissertations, Professional Papers, and Capstones

The Gibbs lab has maintained starvation-selected Drosophila melanogaster for >130 generations. These starvation-selected flies evolved an obese phenotype with a suite of physiological differences compared to control-fed flies. Previous studies have shown that long-term starvation-selected Drosophila contain more lipids, have lower metabolic rates and develop more slowly than controls. This dissertation encompasses 1) Examining the molecular mechanisms contributing to starvation resistance, 2) Functional validation of the candidate plin1 allele, and 3) Rapid physiological and genomic evolution in starvation-selected Drosophila.

Starvation-selected Drosophila survive starvation conditions much longer than control-fed flies. This study took a simple approach to identify possible differences in …

Characterization Of Beryllium Ion Complexation In The Presence Of Biological Buffers Using Isothermal Titration Calorimetry, Guillermo Alexander Ramirez

UNLV Theses, Dissertations, Professional Papers, and Capstones

Be2+ ion is a biologically active metal that is capable of binding to proteins and has been shown to affect various cellular processes. When treated with Be2+, certain cancer cells display cytostatic effects. GSK3β is a regulatory kinase involved in the β-catenin pathway that may be involved in producing these cytostatic effects when Be2+ binds to it. In order to determine binding parameters between Be2+ and GSK3β, isothermal titration calorimetry (ITC) can be utilized. However, titrations at physiological pH cannot be carried out due to Be2+ unique speciation at neutral pH ranges. Significant precipitation occurs at pH 6 and higher …

Robust Cullin-Ring Ligase Function Is Established By A Multiplicity Of Poly-Ubiquitylation Pathways, Spencer Hill, Kurt Reichermeier, Daniel C. Scott, Lorena Samentar, Jasmin Coulombe-Huntington, Luisa Izzi, Xiaojing Tang, Rebeca Ibarra, Thierry Bertomeu, Annie Moridian, Michael J. Sweredoski, Nora Caberoy, Brenda A. Schulman, Frank Sicheri, Mike Tyers, Gary Kleiger

Life Sciences Faculty Research

The cullin-RING ligases (CRLs) form the major family of E3 ubiquitin ligases. The prototypic CRLs in yeast, called SCF enzymes, employ a single E2 enzyme, Cdc34, to build poly-ubiquitin chains required for degradation. In contrast, six different human E2 and E3 enzyme activities, including Cdc34 orthologs UBE2R1 and UBE2R2, appear to mediate SCF-catalyzed substrate polyubiquitylation in vitro. The combinatorial interplay of these enzymes raises questions about genetic buffering of SCFs in human cells and challenges the dogma that E3s alone determine substrate specificity. To enable the quantitative comparisons of SCF-dependent ubiquitylation reactions with physiological enzyme concentrations, mass spectrometry was employed …

The Perplexing Paradox Of Clostridioides (Clostridium) Difficile Infection (Cdi) - Analysis Of Anti-Germinants As Part Of Cdi Prophylaxis, Christopher Yip

UNLV Theses, Dissertations, Professional Papers, and Capstones

Clostridioides (Clostridium) difficile infections (CDI) have become the leading cause of nosocomial antibiotic-associated diarrhea worldwide. Under normal circumstances, bacteria found in the gastrointestinal tract provide a barrier against C. difficile colonization. Upon antibiotic therapy, the protective barrier is lost as the microbial community becomes depleted thus providing the opportunity for C. difficile to colonize the human gut. Exposure to taurocholate, a bile acid produced within the mammalian gastrointestinal tract, causes C. difficile spores to begin their transition, a process known as germination, from metabolically dormant structures to toxin-producing cells. As germination is required for the onset of CDI, anti-germination compounds …

Uncovering New Mechanisms Of Cdc34 And Cullin-Ring Activity, Spencer Hill

UNLV Theses, Dissertations, Professional Papers, and Capstones

Ubiquitylation is a cellular regulatory system found in all eukaryotic cells, which has managed to find a role in most pathways imaginable. The system works fundamentally through the ligation of a small protein known as ubiquitin onto a substrate. Depending on the context of the ubiquitin ligation, the substrate can be directed towards a number of cellular fates, the best-studied being degradation of the substrate. While originally thought of as a signal for cellular disposal units to degrade aberrant proteins, we now know that ubiquitin plays a highly nuanced role in cellular epistasis, controlling everything from the cell cycle to …

Nitric Oxide Is Involved In Heavy Ion-Induced Non-Targeted Effects In Human Fibroblasts, Megumi Hada, Premkumar B. Saganti, Francis A. Cucinotta

Health Physics and Diagnostic Sciences Faculty Research

Previously, we investigated the dose response for chromosomal aberration (CA) for exposures corresponding to less than one particle traversal per cell nucleus by high energy and charge (HZE) particles, and showed that the dose responses for simple exchanges for human fibroblast irradiated under confluent culture conditions were best fit by non-linear models motivated by a non-targeted effect (NTE). Our results suggested that the simple exchanges in normal human fibroblasts have an important NTE contribution at low particle fluence. Nitric oxide (NO) has been reported as a candidate for intercellular signaling for NTE in many studies. In order to estimate the …

An Unexpected Rhenium(Iv)–Rhenium(Vii) Salt: [Co(Nh3)6]3[Reviio4][Reivf6]46h2o, James Louis_Jean, Samudee Mariappan Balasekaran, Adelheid Hagenbach, Frederic Poineau

Chemistry and Biochemistry Faculty Research

The title hydrated salt, tris[hexaamminecobalt(III)] tetraoxidorhenate(VII) tetrakis[hexafluoridorhenate(IV)] hexahydrate, arose unexpectedly due to possible contamination of the K2ReF6 starting material with KReO4. It consists of octahedral [Co(NH3)6] 3+ cation (Co1 site symmetry 1), tetrahedral [ReVIIO4] anions (Re site symmetry 1) and octahedral [ReIVF6] 2 anions (Re site symmetries 1and 3). The [ReF6] 2 octahedral anions (mean Re—F = 1.834 A˚ ), [Co(NH3)6] 3+ octahedral cations (mean Co—N = 1.962 A˚ ), and the [ReO4] tetrahedral anion (mean Re—O = 1.719 A˚ ) are slightly distorted. A network of N—HF hydrogen bonds consolidates the structure. The crystal studied was refined as a …

Acid Sphingomyelinase Regulates The Localization And Trafficking Of Palmitoylated Proteins, Xiahui Xiong, Chia-Fang Lee, Wenjing Li, Jiekai Yu, Linyu Zhu, Yongsoon Kim, Hul Zhang, Hong Sun

Chemistry and Biochemistry Faculty Research

In human, loss of acid sphingomyelinase (ASM/SMPD1) causes Niemann–Pick disease, type A. ASM hydrolyzes sphingomyelins to produce ceramides but protein targets of ASM remain largely unclear. Our mass spectrometry-based proteomic analyses have identified >100 proteins associated with the ASM-dependent, detergent-resistant membrane microdomains (lipid rafts), with >60% of these proteins being palmitoylated, including SNAP23, Src-family kinases Yes and Lyn, and Ras and Rab family small GTPases. Inactivation of ASM abolished the presence of these proteins in the plasma membrane, with many of them trapped in the Golgi. While palmitoylation inhibitors and palmitoylation mutants phenocopied the effects of ASM inactivation, we demonstrated …

Delineation Of Events In Centripetal Migration During Drosophila Oogenesis, Travis Tait Parsons

UNLV Theses, Dissertations, Professional Papers, and Capstones

All multicellular organisms initially start out as a single cell. This cell must use the genetic information encoded in its DNA to multiply in number and build itself into a complex multicellular organism. How this process occurs is the focus of developmental biology, a field that seeks to understand how a combination of genetic information and environmental conditions shape a cell from its beginnings as a zygote all the way to maturity. A fundamental part of this process is the ability of cells to work together in order to build complex tissues and organs. Cells achieve this coordination by using …

Induction Of Met Receptor Tyrosine Kinase Down-Regulation Through Antibody-Mediated Receptor Clustering, Wenjing Li, Adam Dick, Fei Lu, Hong Sun

Chemistry and Biochemistry Faculty Research

The proto-oncoprotein MET is a receptor tyrosine kinase that plays a key role in cancer cell growth and invasion. We have used fluorescence-tagged antibodies to activate MET in live serum-starved glioblastoma cells and monitor the fate of antibody-bound MET receptor in single cell-based assays. We found that the antibodies induced rapid and transient formation of highly polarized MET clusters on the plasma membrane and promoted the activation of MET, resembling the initial effects of binding to its ligand, HGF. However, the antibody-induced clustering and activation of MET led to the rapid removal of the receptor from cell surface and altered …

Starvation Resistance Is Associated With Developmentally Specified Changes In Sleep, Feeding And Metabolic Rate, Elizabeth B. Brown, Melissa E. Slocumb, Milan Szuperak, Arianna Kerbs, Allen G. Gibbs, Matthew S. Kayser, Alex C. Keene

Life Sciences Faculty Research

Food shortage represents a primary challenge to survival, and animals have adapted diverse developmental, physiological and behavioral strategies to survive when food becomes unavailable. Starvation resistance is strongly influenced by ecological and evolutionary history, yet the genetic basis for the evolution of starvation resistance remains poorly understood. The fruit fly Drosophila melanogaster provides a powerful model for leveraging experimental evolution to investigate traits associated with starvation resistance. While control populations only live a few days without food, selection for starvation resistance results in populations that can survive weeks. We have previously shown that selection for starvation resistance results in increased …

Aligning Best Practices In Student Success And Career Preparedness: An Exploratory Study To Establish Pathways To Stem Careers For Undergraduate Minority Students, Kimberly D. Kendricks, Anthony A. Arment, K. V. Nedunuri, Cadance A. Lowell

Journal of Research in Technical Careers

Undergraduate minority retention and graduation rates in STEM disciplines is a nationally recognized challenge for workforce growth and diversification. The Benjamin Banneker Scholars Program (BBSP) was a five-year undergraduate study developed to increase minority student retention and graduation rates at an HBCU. The program structure utilized a family model as a vehicle to orient students to the demands of college. Program activities integrated best K-12 practices and workforce skillsets to increase academic preparedness and career readiness. Findings revealed that a familial atmosphere improved academic performance, increased undergraduate research, and generated positive perceptions of faculty mentoring. Retention rates among BBSP participants …

Proliferating Cell Nuclear Antigen Interacts With The Crl4 Ubiquitin Ligase Subunit Cdt2 In Dna Synthesis-Induced Degradation Of Cdt1, Feng Leng, Lovely Saxena, Nam Hoang, Chunxiao Zhang, Logan Lee, Wenjing Li, Xiaoshan Gong, Fei Lu, Hong Sun, Hui Zhang

Chemistry and Biochemistry Faculty Research

During DNA replication or repair, the DNA polymerase cofactor, proliferating cell nuclear antigen (PCNA), homotrimerizes and encircles the replicating DNA, thereby acting as a DNA clamp that promotes DNA polymerase processivity. The formation of the PCNA trimer is also essential for targeting the replication-licensing protein, chromatin-licensing, and DNA replication factor 1 (CDT1), for ubiquitin-dependent proteolysis to prevent chromosomal DNA re-replication. CDT1 uses its PCNA-interacting peptide box (PIP box) to interact with PCNA, and the CRL4 E3 ubiquitin ligase subunit CDT2 is recruited through the formation of PCNA–CDT1 complexes. However, it remains unclear how CDT1 and many other PIP box–containing proteins …