Biochemistry, Biophysics, and Structural Biology Commons^™

Characterization Of The Roles Of Muscle-Synthesized Brain-Derived Neurotrophic Factor And Presynaptic Tyrosine Receptor Kinase B In Motor Neuron Axonal Transport, Luke A. Vanosdol

All NMU Master's Theses

Brain-derived neurotrophic factor (BDNF) is a small, diffusible protein essential for the development and function of neurons. It is synthesized by many types of tissue, including muscle. BDNF actions are mediated via binding to its receptor, tyrosine receptor kinase B (TrkB). The BDNF-TrkB complex is endocytosed into a specialized vesicle, which induces downstream signaling cascades locally in the dendrites, or, more often, is delivered to the cell soma via retrograde axonal transport, where it modulates gene expression. BDNF activation of TrkB is critical for the initiation of axonal transport, and this cellular process relies on the interaction of numerous adaptor …

A Complex Molecular Switch Directs Stress-Induced Cyclin C Nuclear Release Through Scfgrr1-Mediated Degradation Of Med13., David C Stieg, Stephen D Willis, Vidyaramanan Ganesan, Kai Li Ong, Joseph Scuorzo, Mia Song, Julianne Grose, Randy Strich, Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Departmental Research

In response to oxidative stress, cells decide whether to mount a survival or cell death response. The conserved cyclin C and its kinase partner Cdk8 play a key role in this decision. Both are members of the Cdk8 kinase module, which, with Med12 and Med13, associate with the core mediator complex of RNA polymerase II. In

Contractile Response Of Bovine Lateral Saphenous Vein To Ergotamine Tartrate Exposed To Different Concentrations Of Molecularly Imprinted Polymer, Manoj B. Kudupoje, James L. Klotz, Alexandros Yiannikouris, Karl A. Dawson, Kyle R. Mcleod, Eric S. Vanzant

Animal and Food Sciences Faculty Publications

Ergot alkaloids, in their active isomeric form, affect animal health and performance, and adsorbents are used to mitigate toxicities by reducing bioavailability. Adsorbents with high specificity (molecularly imprinted polymers: MIP) adsorb ergot alkaloids in vitro, but require evaluation for biological implications. Using ex vivo myography, synthetic polymers were evaluated for effects on the bioactivity of ergotamine tartrate (ETA). Polymers were first evaluated using isotherms. Lateral saphenous veins were collected from 17 steers for four independent studies: dose response of ETA, adsorbent dose response, validation of pre-myograph incubation conditions and MIP/ non-molecularly imprinted polymer (NIP) comparison. Norepinephrine normalized percent contractile response …

Mechanisms For Survival And Drug Resistance In Cancer Cells, Matthew B. Utter

Dissertations, Theses, and Capstone Projects

PART I

Prostate cells are hormonally driven to grow and divide. Typical treatments for prostate cancer involve blocking the hormone androgen from activating the androgen receptor (AR) and thus inhibit growth and proliferation of the cancer. Androgen deprivation therapy (ADT) can lead to the selection of cancer cells that grow and divide independently of androgen receptor activation. Prostate cancer cells that are insensitive to androgens commonly display metastatic phenotypes and reduced long-term survival of patients. In this study, we provide evidence that androgen-insensitive prostate cancer cells have elevated phospholipase D (PLD) activity relative to the androgen-sensitive prostate cancer cells. PLD …

Microrna Involvement In The Onset And Progression Of Barrett’S Esophagus: A Systematic Review, Reilly J. Clark, Michael P. Craig, Sangeeta Agrawal, Madhavi Kadakia

Biochemistry and Molecular Biology Faculty Publications

Esophageal adenocarcinoma (EAC) is a highly aggressive malignancy that develops from Barrett's esophagus (BE), an intestinal metaplasia of the distal esophagus. microRNAs (miRNAs), short non-coding regulatory RNAs, are frequently dysregulated in BE and are thought to play key roles in the onset of BE and its progression to EAC. miRNAs thus have potential diagnostic and prognostic value and are increasingly being used as cancer biomarkers. This review summarizes the current literature related to miRNAs that are dysregulated in BE within the context of Hedgehog, Notch, MAPK, NF kappa-B, Wnt and epithelial-mesenchymal transition (EMT) signaling which are thought to drive BE …

Sumo Targeting Of A Stress-Tolerant Ulp1 Sumo Protease, Jennifer Peek, Catherine Harvey, Dreux Gray, Danny Rosenberg, Likhitha Kolla, Reuben Levy-Myers, Rui Yin, Oliver Kerscher, Jonathan L. Mcmurry

Faculty Articles

SUMO proteases of the SENP/Ulp family are master regulators of both sumoylation and desumoylation and regulate SUMO homeostasis in eukaryotic cells. SUMO conjugates rapidly increase in response to cellular stress, including nutrient starvation, hypoxia, osmotic stress, DNA damage, heat shock, and other proteotoxic stressors. Nevertheless, little is known about the regulation and targeting of SUMO proteases during stress. To this end we have undertaken a detailed comparison of the SUMO-binding activity of the budding yeast protein Ulp1 (ScUlp1) and its ortholog in the thermotolerant yeast Kluyveromyces marxianus, KmUlp1. We find that the catalytic UD domains of both ScUlp1 and KmUlp1 …

Crosstalk Among Lncrnas, Micrornas And Mrnas In The Muscle ‘Degradome’ Of Rainbow Trout, Bam Paneru, Ali Ali, Rafet Al-Tobasei, Brett Kenney, Mohamed Salem

Faculty & Staff Scholarship

In fish, protein-coding and noncoding genes involved in muscle atrophy are not fully characterized. In this study, we characterized coding and noncoding genes involved in gonadogenesis-associated muscle atrophy, and investigated the potential functional interplay between these genes. Using RNA- Seq, we compared expression pattern of mRNAs, long noncoding RNAs (lncRNAs) and microRNAs of atrophying skeletal muscle from gravid females and control skeletal muscle from age-matched sterile individuals. A total of 852 mRNAs, 1,160 lncRNAs and 28 microRNAs were differentially expressed (DE) between the two groups. Muscle atrophy appears to be mediated by many genes encoding ubiquitin- proteasome system, autophagy related …

Examination Of Orthologous Genes (Mrub_2518 And B3728, Mrub_2519 And B3727, Mrub_2520 And B3726, Mrub_2521 And B3725) Responsible For Abc Phosphate Transporters In Two Species M. Ruber And E. Coli, Margaret Meyer, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

In this project we investigated the biological function of the genes b3725, b3726, b3727, b3728 and Mrub_2518, Mrub_2519, Mrub_2520 and Mrub_2521 (KEGG map number 02010). We predict that these genes encode the components of a Phosphate ABC transporter: Orthologous genes Mrub_2518 (DNA coordinates 2565359..2566438) and b3728 encodes the periplasmic phosphate binding component; Orthologous genes Mrub_2519 (DNA coordinates 2566499..2567485) and b3727, and Mrub_2520 (DNA coordinates 2567496..2568326) and b3726 encode for the two transmembrane proteins; Orthologous genes Mrub_2521 (DNA coordinates 2568338..2569159) and b3725 encode for the ATP binding protein within the cytoplasm. Within the two species, M. ruber and E. coli, …

Mrub_1325, Mrub_1326, Mrub_1327, And Mrub_1328 Are Orthologs Of B_3454, B_3455, B_3457, B_3458, Respectively Found In Escherichia Coli Coding For A Branched Chain Amino Acid Atp Binding Cassette (Abc) Transporter System, Bennett Tomlin, Adam Buric, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

In this project we investigated the biological function of the genes Mrub_1325, Mrub_1326, Mrub_1327, and Mrub_1328 (KEGG map number 02010). We predict these genes encode components of a Branched Chain Amino Acid ATP Binding Cassette (ABC) transporter: 1) Mrub_1325 (DNA coordinates 1357399-1358130 on the reverse strand) encodes the ATP binding domain; 2) Mrub_1326 (DNA coordinates 1358127-1359899 on the reverse strand) encodes the ATP-binding domain and permease domain; 3) Mrub_1327 (DNA coordinates 1359899-1360930 on the reverse strand) encodes a permease domain; and 4)Mrub_1328 (DNA coordinates 1711022-1712185 on the reverse strand) encodes the substrate binding domain. This system is not predicted to …

Confirmation That Mrub_1751 Is Homologous To E. Coli Xylf, Mrub_1752 Is Homologous To E. Coli Xylh, And Mrub_1753 Is Homologous To E. Coli Xylg, Ben Price, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

In this project we investigated the biological function of the genes Mrub_1751, Mrub_1752 and Mrub_1753 (KEGG map number 02010). We predict these genes encode components of a D-xylose ATP Binding Cassette (ABC) transporter: 1) Mrub_1752 (DNA coordinates 1809004-1810224 on the forward strand) encodes the permease component (aka transmembrane domain), predicted to be an ortholog and 2) Mrub_1753 (DNA coordinates 1810227-1811000 on the forward strand) encodes the ATP-binding domain (aka nucleotide binding domain); and 3) Mrub_1751 (DNA coordinates 1807855-1808892 on the forward strand) encodes the solute binding protein. The ABC-transporter for M. ruber to transport D-xylose is homologous with the transporter …

Mrub_2120, Mrub_2121, Mrub_2122, Mrub_2123 And Mrub_2124 Are Orthologs Of E. Coli Genes B3458, B3457, B3456, B3455 And B3454, Respectively, And Make Up An Operon That Codes For The Branched-Chain Amino Acid Abc Transporter In Meiothermus Ruber Dsm 1279, Aaron Jones, Madelyn Huber, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

In this project we investigated the biological function of the genes Mrub_2120, Mrub_2121, Mrub_2122, Mrub_2123 and Mrub_2124 (KEGG map number 02010). We predict these genes encode components of a branched-chain amino acid ATP Binding Cassette (ABC) transporter: 1) Mrub_2120 (DNA coordinates 2169247-2170416 on the reverse strand) encodes the branched-chain amino acid binding protein that is localized to the periplasm; 2) Mrub_2121 (DNA coordinates 2170433..2171353 on the reverse strand) encodes the first TMD; 3) Mrub_2122 (DNA coordinates 2171365..2172279 on the reverse strand) encodes the second TMD; 4) Mrub_2123 (DNA coordinates 2172276..2173028 on the reverse strand) encodes the first NBD; 5) Mrub_2124 …

Mrub_1675, Mrub_1676, Mrub_1677, And Mrub_1679 Genes Are Orthologs Of B_3458, B_3457, B_3456, And B_3454 Genes In E. Coli, Respectively, Coding For Abc Transporters. Mrub_1678 And B_3455, Though Perform Similar Tasks, Are Not Orthologous, Ravi Patel, Alaina Hofmann, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

In this project we investigated the biological function of the genes Mrub_1675, Mrub_1676, Mrub_1677, and Mrub_1679 (KEGG map number 02010). We predict these genes encode components of a Branched chain amino acid (ABC) transporter: Mrub_1675 (DNA coordinates 1711022..1712185 on the reverse strand) encodes the permease component, Mrub_1676 (DNA coordinates 1712313..1713170) encodes for the NBD (aka nucleotide binding domain), Mrub_1677 (DNA coordinates 1713167..1714075 on the reverse strand) encodes the NBD (aka nucleotide binding domain), Mrub_1678 (DNA coordinates 1713167..1714075 on the reverse strand) encodes the TMD (aka transmembrane domain) and Mrub_1679 (DNA coordinates 1714781..1715485 on the reverse strand) encodes …

Quantum Confined Peptide Assemblies With Tunable Visible To Near-Infrared Spectral Range, Kai Tao, Zhen Fan, Leming Sun, Pandeeswar Makam, Zhen Tian, Mark Ruegsegger, Shira Shaham-Niv, Derek Hansford, Ruth Aizen, Zui Pan, Scott Galster, Jianjie Ma, Fan Yuan, Mingsu Si, Songnan Qu, Mingjun Zhang, Ehud Gazit, Junbai Li

Faculty & Staff Scholarship

Quantum confined materials have been extensively studied for photoluminescent applica- tions. Due to intrinsic limitations of low biocompatibility and challenging modulation, the utilization of conventional inorganic quantum confined photoluminescent materials in bio- imaging and bio-machine interface faces critical restrictions. Here, we present aromatic cyclo-dipeptides that dimerize into quantum dots, which serve as building blocks to further self-assemble into quantum confined supramolecular structures with diverse morphologies and photoluminescence properties. Especially, the emission can be tuned from the visible region to the near-infrared region (420 nm to 820 nm) by modulating the self-assembly process. Moreover, no obvious cytotoxic effect is observed for …

Integrated Analysis Of Lncrna And Mrna Expression In Rainbow Trout Families Showing Variation In Muscle Growth And Fillet Quality Traits, Ali Ali, Rafet Al-Tobasei, Brett Kenney, Timothy D. Leeds, Mohamed Salem

Faculty & Staff Scholarship

Muscle yield and quality traits are important for the aquaculture industry and consumers. Genetic selection for these traits is difficult because they are polygenic and result from multifactorial interactions. To study the genetic architecture of these traits, phenotypic characterization of whole body weight (WBW), muscle yield, fat content, shear force and whiteness were measured in ~500 fish representing 98 families from a growth-selected line. RNA-Seq was used to sequence the muscle transcriptome of different families exhibiting divergent phenotypes for each trait. We have identified 240 and 1,280 differentially expressed (DE) protein-coding genes and long noncoding RNAs (lncRNAs), respectively, in fish …

Graphene Nanoplatelets-Sericin Surface-Modified Gum Alloy For Improved Biological Response, Valentina Mitran, Valentina Dinca, Raluca Ion, Vasile D. Cojocaru, Patricia Neacsu, Cerasela Zoica Dinu, Laurentiu Rusen, Simona Brajnicov, Anca Bonciu, Maria Dinescu, Doina Raducanu, Ioan Dan

Faculty & Staff Scholarship

In this study a “Gum Metal” titanium-based alloy, Ti-31.7Nb-6.21Zr-1.4Fe-0.16O, was synthesized by melting and characterized in order to evaluate its potential for biomedical applications. The results showed that the newly developed alloy presents a very high strength, high plasticity and a low Young's modulus relative to titanium alloys currently used in medicine. For further bone implant applications, the newly synthesized alloy was surface modified with graphene nanoplatelets (GNP), sericin (SS) and graphene nanoplatelets/sericine (GNP–SS) composite films via Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique. The characterization of each specimen was monitored by scanning electron microscopy (SEM), atomic force microscopy (AFM), …

Multilevel Structural Equation Modeling Of Students’ Dietary Intentions/Behaviors, Bmi, And The Healthfulness Of Convenience Stores, Tanya Horacek, Elif Dede Yildirim, Kendra Kattelmann, Carol Byrd-Bredbenner, Onikia Brown, Sarah Colby, Geoffrey Greene, Sharon Hoerr, Tandalayo Kidd, Mallory Koenings, Jesse Morrell, Melissa D. Olfert, Beatrice Phillips, Karla Shelnutt, Adrienne White

Faculty & Staff Scholarship

Background: When dietary behaviors are habitual, intentions are low, and environmental cues, such as the consumer food environment, might guide behavior. How might intentions to eat healthily and ultimately actual dietary behaviors, be influenced by the consumer food environment (including the availability and affordability of healthy foods) in convenience stores? This study will determine pathways between the healthfulness of convenience stores and college students’ dietary intentions/behaviors, and body mass index (BMI). Methods: Through multilevel structural equation modeling, a comparison was made of students’ healthful meal intentions (HMI); intake (fruits/vegetables, %kcal/fat, sugar-sweetened beverages (SSBs) and whole-grains); and measured BMI; as well …

The Igf2/Igf1r/Nanog Signaling Pathway Regulates The Proliferation Of Acute Myeloid Leukemia Stem Cells., Dan-Dan Xu, Ying Wang, Peng-Jun Zhou, Shu-Rong Qin, Rong Zhang, Yi Zhang, +Several Additional Authors

Biochemistry and Molecular Medicine Faculty Publications

Acute myeloid leukemia is an aggressive disease characterized by clonal proliferation and differentiation into immature hematopoietic cells of dysfunctional myeloid precursors. Accumulating evidence shows that CD34+CD38- leukemia stem cells (LSCs) are responsible for drug resistance, metastasis, and relapse of leukemia. In this study, we found that Nanog, a transcription factor in stem cells, is significantly overexpressed in CD34+ populations from patients with acute myeloid leukemia and in LSCs from leukemia cell lines. Our data demonstrate that the knockdown of Nanog inhibited proliferation and induced cell cycle arrest and cell apoptosis. Moreover, Nanog silencing suppressed the leukemogenesis of LSCs in mice. …

Superresolved Three-Dimensional Analysis Of The Spatial Arrangement Of The Human Immunodeficiency Virus Type-1 (Hiv-1) Envelope Glycoprotein At Sites Of Viral Assembly, Carmen Anne Buttler

Electronic Theses and Dissertations

Human Immunodeficiency Virus type 1 (HIV-1) replicates by forcing infected host cells to produce new virus particles, which assemble form protein components on the inner leaflet of the host cell's plasma membrane. This involves incorporation of the essential viral envelope glycoprotein (Env) into a structural lattice of viral Gag proteins. The mechanism of Env recruitment and incorporation is not well understood. To better define this process, we seek to describe the timing of Env-Gag encounters during particle assembly by measuring angular positions of Env proteins about the surfaces of budding particles. Using three-dimensional superresolution microscopy, we show that Env distributions …

Association Of Two Foxp3 Polymorphisms With Breast Cancer In Chinese Han Women, Wenge Zhu, +Several Additional Authors

Biochemistry and Molecular Medicine Faculty Publications

Background

Forkhead box P3 (FOXP3) is a key gene in the immune system which also plays a role in tumor development. This study aims to explore the association of two FOXP3 polymorphisms (rs3761548 and rs3761549) with susceptibility to breast cancer (BC).

Method

A case–control study was conducted, involving 560 patients and 583 healthy individuals from the Chinese Han population. The genotypes of FOXP3 polymorphisms were detected using the Sequenom MassARRAY method. The association between FOXP3 polymorphisms and BC risk was evaluated using a χ2 test with an odds ratio (OR) and 95% confidence intervals (95% CIs) under six …

Studies Of Norspermidine Uptake In Drosophila Suggest The Existence Of Multiple Polyamine Transport Pathways, Michael Dieffenbach

Honors Undergraduate Theses

Polyamines are a class of essential nutrients involved in many basic cellular processes such as gene expression, cell proliferation, and apoptosis. Without polyamines, cell growth is delayed or halted. Cancerous cells require an abundance of polyamines through a combination of synthesis and transport from the extracellular environment. An FDA-approved drug, D,L-α-difluoromethylornithine (DFMO), blocks polyamine synthesis but is ineffective at inhibiting cell growth due to polyamine transport. Thus, there is a need to develop drugs that inhibit polyamine transport to use in combination with DFMO. Surprisingly, little is known about the polyamine transport system in humans and other eukaryotes. Understanding the …

Biosynthetic Mechanism Of The Antibiotic Capuramycin, Erfu Yan

Theses and Dissertations--Pharmacy

A-102395 is a member of the capuramycin family of antibiotics which was isolated from the culture broth of Amycolatopsis sp. SANK 60206. A-102339 is structurally classified as a nucleoside antibiotic, which like all members of the capuramycin family, inhibits bacterial MraY (translocase I) with IC₅₀ of 11 nM which is the lowest among the capuramycin family. A semisynthetic derivative of capuramycin is currently in clinical trials as an antituberculosis antibiotic, suggesting high potential for using A-102395 as a starting point for new antibiotic discovery. In contrast to other capuramycins, A-102395 has a unique arylamine-containing polyamide side chain. The biosynthetic …

Role Of Glycerol-3-Phosphate Permeases In Plant Defense, Juliana Moreira Soares

Theses and Dissertations--Plant Pathology

Systemic acquired resistance (SAR) is a type of plant defense mechanism that is induced after a localized infection and confers broad-spectrum immunity against related or unrelated pathogens. During SAR, a number of chemical signals and proteins generated at the site of primary infection travel to the uninfected tissues and are thought to alert the distal sites against secondary infections. Glycerol-3-phosphate (G3P) is one of the chemical signals that play an important role in SAR. G3P is synthesized in the cytosol and chloroplasts via the enzymatic activities of G3P Dehydrogenase (G3Pdh) or Glycerol Kinase (GK). Interestingly, a mutation in three of …

Validating Functional Mechanisms For Non-Coding Genetic Variants Associated With Complex Traits, Cynthia Ann Kalita

Wayne State University Dissertations

Genome-wide association studies (GWAS) have identified a large number of genetic variants associated with disease as well as normal phenotypic variation for complex traits. However challenges remain in determining the functional relevance of human DNA sequence variants. Even after fine mapping, most variants are located in non-coding regions making it difficult to infer mechanisms linking individual genetic variants with the disease trait. In addition, we do not know under which environmental conditions the sequence variants have a functional impact, and whether they become one of many factors involved in complex phenotypes at the organismal level.

Chapter 1 describes computational methods …

Asymmetric Patterns Of Small Molecule Transport After Nanosecond And Microsecond Electropermeabilization, Esin B. Sözer, C. Florencia Pocetti, P. Thomas Vernier

Bioelectrics Publications

Imaging of fluorescent small molecule transport into electropermeabilized cells reveals polarized patterns of entry, which must reflect in some way the mechanisms of the migration of these molecules across the compromised membrane barrier. In some reports, transport occurs primarily across the areas of the membrane nearest the positive electrode (anode), but in others cathode-facing entry dominates. Here we compare YO-PRO-1, propidium, and calcein uptake into U-937 cells after nanosecond (6 ns) and microsecond (220 µs) electric pulse exposures. Each of the three dyes exhibits a different pattern. Calcein shows no preference for anode- or cathode-facing entry that is detectable with …

The Effects Of Oxidative Stress On P75ntr Signaling In Dopaminergic Neurons, Cassandra Marie Escobedo

Online Theses and Dissertations

The p75 neurotrophin receptor (p75NTR) is responsible for implementing cellular death during embryonic development and in response to cellular injury. The receptor has been recognized as a contributor of neurodegeneration in numerous pathological conditions. Cleavage of p75NTR by Tumor Necrosis Factor converting enzyme (TACE) and γ-secretase has been observed to be associated with an increase in neurodegeneration. In a previous study, p75NTR was discovered to become activated in sympathetic neurons in response to oxidative stress induced by 4-hydroxynonenal (HNE) in a ligand-independent mechanism. Furthermore, cleavage of the receptor was demonstrated to contribute to the death of sympathetic neurons following oxidative …

Expression And Function Of Nuclear Receptor Coactivator 4 Isoforms In Transformed Endometriotic And Malignant Ovarian Cells, Stephanie Rockfield, Idhaliz Flores, Meera Nanjundan

Molecular Biosciences Faculty Publications

Iron is proposed to contribute to the transition from endometriosis to specific subtypes of ovarian cancers (OVCAs). Regulation of intracellular iron occurs via a ferritinophagic process involving NCOA4 (Nuclear Receptor Coactivator 4), represented by two major isoforms (NCOA4α and NCOA4β), whose contribution to ovarian cancer biology remains uninvestigated. We thus generated transformed endometriotic cells (via HRAS^V12A, c-MYC^T58A, and p53 inactivation) whose migratory potential was increased in response to conditioned media from senescent endometriotic cells. We identified elevated NCOA4 mRNA in transformed endometriotic cells (relative to non-transformed). Knockdown of NCOA4 increased ferritin heavy chain (FTH1) and p21 …

Mbd2-Cp2c Loop Drives Adult-Type Globin Gene Expression And Definitive Erythropoiesis, Min Young Kim, Ji Sook Kim, Seung Han Son, Chang Su Lim, Hea Young Eum, Dae Hyun Ha, Mi Ae Park, Eun Jung Baek, Buom-Yong Ryu, Ho Chul Kang, Vladimir N. Uversky, Chul Geun Kim

Molecular Biosciences Faculty Publications

During hematopoiesis, red blood cells originate from the hematopoietic stem cell reservoir. Although the regulation of erythropoiesis and globin expression has been intensively investigated, the underlining mechanisms are not fully understood, including the interplay between transcription factors and epigenetic factors. Here, we uncover that the Mbd2-free NuRD chromatin remodeling complex potentiates erythroid differentiation of proerythroblasts via managing functions of the CP2c complexes. We found that both Mbd2 and Mbd3 expression is downregulated during differentiation of MEL cells in vitro and in normal erythropoiesis in mouse bone marrow, and Mbd2 downregulation is crucial for erythropoiesis. In uninduced MEL cells, the Mbd2-NuRD …

Yeast Lifespan Variation Correlates With Cell Growth And Sir2 Expression, Jessica T. Smith, Jill W. White, Huzefa Dungrawala, Hui Hua, Brandt L. Schneider

Molecular Biosciences Faculty Publications

Isogenic wild type yeast cells raised in controlled environments display a significant range of lifespan variation. Recent microfluidic studies suggest that differential growth or gene expression patterns may explain some of the heterogeneity of aging assays. Herein, we sought to complement this work by similarly examining a large set of replicative lifespan data from traditional plate assays. In so doing, we reproduced the finding that short-lived cells tend to arrest at senescence with a budded morphology. Further, we found that wild type cells born unusually small did not have an extended lifespan. However, large birth size and/or high inter-generational growth …

Radx Modulates Rad51 Activity To Control Replication Fork Protection, Kamakoti P. Bhat, Archana Krishnamoorthy, Huzefa Dungrawala, Edwige B. Garcin, Mauro Modesti, David Cortez

Molecular Biosciences Faculty Publications

RAD51 promotes homologous recombination repair (HR) of double-strand breaks and acts during DNA replication to facilitate fork reversal and protect nascent DNA strands from nuclease digestion. Several additional HR proteins regulate fork protection by promoting RAD51 filament formation. Here, we show that RADX modulates stalled fork protection by antagonizing RAD51. Consequently, silencing RADX restores fork protection in cells deficient for BRCA1, BRCA2, FANCA, FANCD2, or BOD1L. Inactivating RADX prevents both MRE11- and DNA2-dependent fork degradation. Furthermore, RADX overexpression causes fork degradation that is dependent on these nucleases and fork reversal. The amount of RAD51 determines the fate of stalled replication …

Septal Secretion Of Protein A In Staphylococcus Aureus Requires Seca And Lipoteichoic Acid Synthesis, Wenqi Yu, Dominique Missiakas, Olaf Schneewind

Molecular Biosciences Faculty Publications

Surface proteins of Staphylococcus aureus are secreted across septal membranes for assembly into the bacterial cross-wall. This localized secretion requires the YSIRK/GXXS motif signal peptide, however the mechanisms supporting precursor trafficking are not known. We show here that the signal peptide of staphylococcal protein A (SpA) is cleaved at the YSIRK/GXXS motif. A SpA signal peptide mutant defective for YSIRK/GXXS cleavage is also impaired for septal secretion and co-purifies with SecA, SecDF and LtaS. SecA depletion blocks precursor targeting to septal membranes, whereas deletion of secDF diminishes SpA secretion into the cross-wall. Depletion of LtaS blocks lipoteichoic acid synthesis and …