DOCSLIB.ORG

When DNA Meets RNA

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
When DNA Meets RNA cells Review The Ultimate (Mis)match: When DNA Meets RNA Benoit Palancade 1,* and Rodney Rothstein 2,* 1 Institut Jacques Monod, Université de Paris, CNRS, F-75006 Paris, France 2 Department of Genetics & Development, Columbia University Irving Medical Center, New York, NY 10032, USA * Correspondence: [email protected] (B.P.); [email protected] (R.R.) Abstract: RNA-containing structures, including ribonucleotide insertions, DNA:RNA hybrids and R-loops, have recently emerged as critical players in the maintenance of genome integrity. Strikingly, different enzymatic activities classically involved in genome maintenance contribute to their gen- eration, their processing into genotoxic or repair intermediates, or their removal. Here we review how this substrate promiscuity can account for the detrimental and beneficial impacts of RNA in- sertions during genome metabolism. We summarize how in vivo and in vitro experiments support the contribution of DNA polymerases and homologous recombination proteins in the formation of RNA-containing structures, and we discuss the role of DNA repair enzymes in their removal. The diversity of pathways that are thus affected by RNA insertions likely reflects the ancestral function of RNA molecules in genome maintenance and transmission. Keywords: DNA repair; genetic recombination; genetic stability; transcription; RNA; ribonucleotide; DNA:RNA hybrid; R-loop 1. Introduction Citation: Palancade, B.; Rothstein, R. The Ultimate (Mis)match: When Among the many scientific contributions that Miro Radman has made to our under- DNA Meets RNA. Cells 2021, 10, 1433. standing of genome biology, his work on the SOS response and mismatch repair stands https://doi.org/10.3390/cells10061433 out amongst the most visionary. Combining observations that he and his colleagues made using bacteria and their phages, he outlined the main features of the cellular response to Academic Editors: Bernard S. Lopez DNA damage and foreshadowed its importance for genetic stability [1–4]. An important and Ivan Matic concept arising from these pioneering studies is that damage to the genome can be tolerated by calling into play the cellular machineries that ensure viability, even at the expense of Received: 12 May 2021 genetic integrity. Accepted: 5 June 2021 During the past several years, an increasing number of obstacles to DNA-related Published: 8 June 2021 transactions was found to similarly trigger DNA repair and tolerance mechanisms. Among them, RNA-containing structures have recently caught the attention of DNA biologists, as Publisher’s Note: MDPI stays neutral addressed in several recent excellent reviews [5–10]. These range from single ribonucleotide with regard to jurisdictional claims in insertions to RNA stretches, DNA:RNA hybrids and R-loops, in which a single-stranded published maps and institutional affil- DNA is displaced (Figure1). Such structures are observed in diverse species and represent iations. a significant fraction of their genomes: for example, ribonucleotides are incorporated in newly synthesized DNA at an overall rate of ~1:1000 nucleotides [11] and R-loops occupy approximately 5% of the human genome [12]. It has become increasingly clear that these structures are relevant for genome integrity: on the one hand, genetic screens have high- Copyright: © 2021 by the authors. lighted the importance of RNA metabolism factors in the DNA damage response [13–16], Licensee MDPI, Basel, Switzerland. and on the other hand, factors classically associated with DNA repair or genome main- This article is an open access article tenance handle RNA-containing substrates in vitro [17–20]. Finally, dedicated enzymes distributed under the terms and can specifically process DNA/RNA hybrid structures, as exemplified by the H class of conditions of the Creative Commons nucleases (RNase H1 and H2 in eukaryotes), which hydrolyze RNA moieties in DNA:RNA Attribution (CC BY) license (https:// duplexes [21]. creativecommons.org/licenses/by/ 4.0/). Cells 2021, 10, 1433. https://doi.org/10.3390/cells10061433 https://www.mdpi.com/journal/cells Cells 2021, 10, x FOR PEER REVIEW 2 of 16 Here, we review evidence obtained from in vivo studies in light of findings arising from in vitro experiments and summarize: (i) how cellular enzymes involved in DNA me- tabolism recognize, utilize or tolerate RNA-containing substrates, and (ii) how this sub- Cells 2021, 10, 1433 strate promiscuity can either trigger the generation of genotoxic structures, or impact 2their of 16 repair. FigureFigure 1. TheThe variety variety of RNA-containing struct structuresures in the genome. Different Different types of ribonucleotide- or RNA-containing structuresstructures are are represented in orange. The The enzymes enzymes with with reported reported contributions contributions to to th theireir generation generation or or removal removal are are listed listed in in blueblue and and magenta, respectively, respectively, and the repair pathways with which they are associated ar aree italicized. The The orange and greygrey arrows arrows indicate indicate the the direction direction of of RNA RNA and and DNA DNA synthesis, synthesis, respectively. respectively. RNAP, RNAP, RNA polymerase. ( (aa),), Ribonucleotide Ribonucleotide incorporationincorporation during during DNA DNA replication. replication. For For simplicity, simplicity, only only one one branch branch of of the the replication replication fork fork is is represented. represented. ( (bb),), R-loop R-loop formationformation and and resolution. resolution. (c (),c ),DNA:RNA DNA:RNA hybrid hybrid accumulation accumulation at DSBs. at DSBs. (d), (RNA-templatedd), RNA-templated DNA DNA repair. repair. The cDNA The cDNA pro- duced upon reverse-transcription can also be used in homology-directed repair in a Rad51- and Rad52-dependent process produced upon reverse-transcription can also be used in homology-directed repair in a Rad51- and Rad52-dependent (not depicted). See text for details. process (not depicted). See text for details. 2. WhenHere, DNA we reviewPolymerases evidence Meet obtained Ribonucleotides from in vivo studies in light of findings arising 2.1.from DNAin vitro Polymerasesexperiments Can Use and rNTPs summarize: during DNA (i) how Synthesis cellular enzymes involved in DNA metabolismSince DNA recognize, polymerases utilize are or generally tolerate RNA-containingunable to catalyze substrates, de novo DNA and synthesis, (ii) how thisthe initiationsubstrate of promiscuity DNA replication can either requires trigger the the activity generation of DNA-dependent of genotoxic structures, RNA polymerases, or impact ortheir primases, repair. which utilize ribonucleotides triphosphate (rNTPs) to synthesize short, ~10 nt-long RNA primers, providing a free 3′ hydroxyl for further leading and lagging strand 2. When DNA Polymerases Meet Ribonucleotides elongation. Notably, replicative DNA polymerases (Pol α, Pol δ, and Pol ε), despite having 2.1. DNA Polymerases Can Use rNTPs during DNA Synthesis a steric-gate residue favoring dNTP selection at their nucleotide binding pocket, can also incorporateSince DNA rNMPs polymerases into newly are synthesized generally unableDNA, as to highlighted catalyze de novoby inDNA vitro synthesis,studies ([11]; the Figureinitiation 1a). of Even DNA with replication rNMP incorporation requires the activity disfavored, of DNA-dependent the high cellular RNA concentration polymerases, of rNTPsor primases, compared which to utilizedNTPs ribonucleotides results in rates triphosphateof ribonucleotide (rNTPs) misincorporation to synthesize short, within ~10 nas- nt- 0 centlong DNA RNA from primers, ~1:600 providing to ~1:5000 a freedepending 3 hydroxyl on the for DNA further polymerase leading andconsidered lagging [11,22]. strand Thus,elongation. rNMP Notably, insertion replicative represents DNA a major polymerases error that (Poloccursα, Polduringδ, and DNA Pol replication,"), despite havingwhich hasa steric-gate been confirmed residue by favoring genome-wide dNTP selection mapping at [23]. their nucleotide binding pocket, can also incorporate rNMPs into newly synthesized DNA, as highlighted by in vitro studies ([11]; Figure1a). Even with rNMP incorporation disfavored, the high cellular concentration of rNTPs compared to dNTPs results in rates of ribonucleotide misincorporation within nascent DNA from ~1:600 to ~1:5000 depending on the DNA polymerase considered [11,22]. Thus, rNMP insertion represents a major error that occurs during DNA replication, which has been confirmed by genome-wide mapping [23]. Cells 2021, 10, 1433 3 of 16 2.2. Recognition of Embedded Ribonucleotides: Genotoxicity vs. Tolerance The insertion of rNMPs in the genome enhances DNA reactivity, favors alkali cleavage, and causes backbone distortions, with possible repercussions on DNA-related transactions, such as replication and chromatin assembly [24]. In view of their potentially deleterious effects, genome-embedded rNMPs are efficiently removed by ribonucleotide excision repair (RER), an error-free pathway that relies on ribonucleotide recognition and excision by RNase H2, which also removes the RNA stretches generated by primase activity [24]. Alternatively, in the absence of RNase H2, ribonucleotide insertion leads to topoisomerase I-dependent cleavage, eventually leading to short deletions in repeated sequences, as revealed by in vitro and in vivo studies [25,26]. Furthermore, the accumulation of rNMPs insertions in the genome causes replication stress and genetic instability, as shown by
Load more

Recommended publications
  • Transcription-Replication Collisions—A Series of Unfortunate Events
    biomolecules Review Transcription-Replication Collisions—A Series of Unfortunate Events Commodore St Germain 1,2,*, Hongchang Zhao 2 and Jacqueline H. Barlow 2,* 1 School of Mathematics and Science, Solano Community College, 4000 Suisun Valley Road, Fairfield, CA 94534, USA 2 Department of Microbiology and Molecular Genetics, University of California Davis, One Shields Avenue, Davis, CA 95616, USA; [email protected] * Correspondence: [email protected] (C.S.G.); [email protected] (J.H.B.) Abstract: Transcription-replication interactions occur when DNA replication encounters genomic regions undergoing transcription. Both replication and transcription are essential for life and use the same DNA template making conflicts unavoidable. R-loops, DNA supercoiling, DNA secondary structure, and chromatin-binding proteins are all potential obstacles for processive replication or transcription and pose an even more potent threat to genome integrity when these processes co-occur. It is critical to maintaining high fidelity and processivity of transcription and replication while navigating through a complex chromatin environment, highlighting the importance of defining cellular pathways regulating transcription-replication interaction formation, evasion, and resolution. Here we discuss how transcription influences replication fork stability, and the safeguards that have evolved to navigate transcription-replication interactions and maintain genome integrity in mammalian cells. Keywords: DNA replication; transcription; R-loops; replication stress Citation: St Germain, C.; Zhao, H.; Barlow, J.H. Transcription-Replication Collisions—A Series of Unfortunate Events. Biomolecules 2021, 11, 1249. 1. Introduction https://doi.org/10.3390/ From bacteria to humans, transcription has been identified as a source of genome biom11081249 instability, initially observed as spontaneous recombination referred to as transcription- associated recombination (TAR) [1].
    [Show full text]
  • Nucleoporin TPR Is an Integral Component of the TREX-2 Mrna Export Pathway
    ARTICLE https://doi.org/10.1038/s41467-020-18266-2 OPEN Nucleoporin TPR is an integral component of the TREX-2 mRNA export pathway Vasilisa Aksenova1, Alexandra Smith1, Hangnoh Lee1, Prasanna Bhat 2, Caroline Esnault3, Shane Chen1, James Iben4, Ross Kaufhold1, Ka Chun Yau 1, Carlos Echeverria1, Beatriz Fontoura 2, Alexei Arnaoutov1 & ✉ Mary Dasso 1 Nuclear pore complexes (NPCs) are important for cellular functions beyond nucleocyto- 1234567890():,; plasmic trafficking, including genome organization and gene expression. This multi-faceted nature and the slow turnover of NPC components complicates investigations of how indi- vidual nucleoporins act in these diverse processes. To address this question, we apply an Auxin-Induced Degron (AID) system to distinguish roles of basket nucleoporins NUP153, NUP50 and TPR. Acute depletion of TPR causes rapid and pronounced changes in tran- scriptomic profiles. These changes are dissimilar to shifts observed after loss of NUP153 or NUP50, but closely related to changes caused by depletion of mRNA export receptor NXF1 or the GANP subunit of the TRanscription-EXport-2 (TREX-2) mRNA export complex. More- over, TPR depletion disrupts association of TREX-2 subunits (GANP, PCID2, ENY2) to NPCs and results in abnormal RNA transcription and export. Our findings demonstrate a unique and pivotal role of TPR in gene expression through TREX-2- and/or NXF1-dependent mRNA turnover. 1 Division of Molecular and Cellular Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. 2 Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. 3 Bioinformatics and Scientific Programming Core, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20879, USA.
    [Show full text]
  • Non-Canonical Functions of the Bacterial Sos Response
    University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2019 Non-Canonical Functions Of The aB cterial Sos Response Amanda Samuels University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Microbiology Commons Recommended Citation Samuels, Amanda, "Non-Canonical Functions Of The aB cterial Sos Response" (2019). Publicly Accessible Penn Dissertations. 3253. https://repository.upenn.edu/edissertations/3253 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/3253 For more information, please contact [email protected]. Non-Canonical Functions Of The aB cterial Sos Response Abstract DNA damage is a pervasive environmental threat, as such, most bacteria encode a network of genes called the SOS response that is poised to combat genotoxic stress. In the absence of DNA damage, the SOS response is repressed by LexA, a repressor-protease. In the presence of DNA damage, LexA undergoes a self-cleavage reaction relieving repression of SOS-controlled effector genes that promote bacterial survival. However, depending on the bacterial species, the SOS response has an expanded role beyond DNA repair, regulating genes involved in mutagenesis, virulence, persistence, and inter-species competition. Despite a plethora of research describing the significant consequences of the SOS response, it remains unknown what physiologic environments induce and require the SOS response for bacterial survival. In Chapter 2, we utilize a commensal E. coli strain, MP1, and established that the SOS response is critical for sustained colonization of the murine gut. Significantly, in evaluating the origin of the genotoxic stress, we found that the SOS response was nonessential for successful colonization in the absence of the endogenous gut microbiome, suggesting that competing microbes might be the source of genotoxic stress.
    [Show full text]
  • HHS Public Access Author Manuscript
    HHS Public Access Author manuscript Author Manuscript Author ManuscriptGenet Epidemiol Author Manuscript. Author Author Manuscript manuscript; available in PMC 2016 June 01. Published in final edited form as: Genet Epidemiol. 2015 December ; 39(8): 664–677. doi:10.1002/gepi.21932. Multiple SNP-sets Analysis for Genome-wide Association Studies through Bayesian Latent Variable Selection Zhaohua Lu, Hongtu Zhu, Rebecca C Knickmeyer, Patrick F. Sullivan, Williams N. Stephanie, and Fei Zou for the Alzheimer’s Disease Neuroimaging Initiative* Departments of Biostatistics, Psychiatry, and Genetics and Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA Abstract The power of genome-wide association studies (GWAS) for mapping complex traits with single SNP analysis may be undermined by modest SNP effect sizes, unobserved causal SNPs, correlation among adjacent SNPs, and SNP-SNP interactions. Alternative approaches for testing the association between a single SNP-set and individual phenotypes have been shown to be promising for improving the power of GWAS. We propose a Bayesian latent variable selection (BLVS) method to simultaneously model the joint association mapping between a large number of SNP-sets and complex traits. Compared to single SNP-set analysis, such joint association mapping not only accounts for the correlation among SNP-sets, but also is capable of detecting causal SNP- sets that are marginally uncorrelated with traits. The spike-slab prior assigned to the effects of SNP-sets can greatly reduce the dimension of effective SNP-sets, while speeding up computation. An efficient MCMC algorithm is developed. Simulations demonstrate that BLVS outperforms several competing variable selection methods in some important scenarios.
    [Show full text]
  • DNA Repair from Wikipedia.Org
    DNA repair From Wikipedia, the free encyclopedia (Redirected from Dna repair) Jump to: navigation, search For the journal, see DNA Repair (journal). DNA damage resulting in multiple broken chromosomes DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many as 1 million individual molecular lesions per cell per day.[1] Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes. Other lesions induce potentially harmful mutations in the cell's genome, which affect the survival of its daughter cells after it undergoes mitosis. Consequently, the DNA repair process is constantly active as it responds to damage in the DNA structure. When normal repair processes fail, and when cellular apoptosis does not occur, irreparable DNA damage may occur, including double-strand breaks and DNA crosslinkages.[2][3] The rate of DNA repair is dependent on many factors, including the cell type, the age of the cell, and the extracellular environment. A cell that has accumulated a large amount of DNA damage, or one that no longer effectively repairs damage incurred to its DNA, can enter one of three possible states: 1. an irreversible state of dormancy, known as senescence 2. cell suicide, also known as apoptosis or programmed cell death 3. unregulated cell division, which can lead to the formation of a tumor that is cancerous The DNA repair ability of a cell is vital to the integrity of its genome and thus to its normal functioning and that of the organism.
    [Show full text]
  • Lecture 9.Pdf
    Lecture-9 M.Sc 2nd Semester (Environmental Microbiology) Paper EM-202: Microbial physiology and adaptation Unit IV: SOS Inducible Repair Mechanism Against UV Induced Damage The SOS Response • The SOS response is the term used to describe changes in gene expression in E. coli in other bacteria in response to extensive DNA damage. The prokaryotic SOS system is regulated by two main protien i.e. Lex A and Rec A. •Despite having multiple repair system, sometimes the damage to an organism’s DNA is so great that the normal repair mechanisms just described cannot repair all the damage. As a result, DNA synthesis stops completely. In such situations, a global control network called the SOS response is activated. •The SOS response is known to be widespread in the Bacteria domain, but it is mostly absent in some bacterial phyla, like the Spirochetes. •The SOS response, like recombination repair, is dependent on the activity of the RecA and Lex A protein . •. The most common cellular signals activating the SOS response are regions of single-stranded DNA (ssDNA), arising from stalled replication fork or double-strand breaks, which are processed by DNA helicase to separate the two DNA strands. In the initiation step, RecA protein binds to ssDNA in an ATP hydrolysis driven reaction creating RecA–ssDNA filaments. •RecA binds to single or double stranded DNA breaks and gaps generated by cessation of DNA synthesis. RecA binding initiates recombination repair. •RecA–ssDNA filaments activate LexA auto protease activity, which ultimately leads to cleavage of LexA dimer and subsequent LexA degradation. •The loss of LexA repressor induces transcription of the SOS genes and allows for further signal induction, inhibition of cell division and an increase in levels of proteins responsible for damage processing.
    [Show full text]
  • Bioinformatics Tools for the Analysis of Gene-Phenotype Relationships Coupled with a Next Generation Chip-Sequencing Data Processing Pipeline
    Bioinformatics Tools for the Analysis of Gene-Phenotype Relationships Coupled with a Next Generation ChIP-Sequencing Data Processing Pipeline Erinija Pranckeviciene Thesis submitted to the Faculty of Graduate and Postdoctoral Studies in partial fulfillment of the requirements for the Doctorate in Philosophy degree in Cellular and Molecular Medicine Department of Cellular and Molecular Medicine Faculty of Medicine University of Ottawa c Erinija Pranckeviciene, Ottawa, Canada, 2015 Abstract The rapidly advancing high-throughput and next generation sequencing technologies facilitate deeper insights into the molecular mechanisms underlying the expression of phenotypes in living organisms. Experimental data and scientific publications following this technological advance- ment have rapidly accumulated in public databases. Meaningful analysis of currently avail- able data in genomic databases requires sophisticated computational tools and algorithms, and presents considerable challenges to molecular biologists without specialized training in bioinfor- matics. To study their phenotype of interest molecular biologists must prioritize large lists of poorly characterized genes generated in high-throughput experiments. To date, prioritization tools have primarily been designed to work with phenotypes of human diseases as defined by the genes known to be associated with those diseases. There is therefore a need for more prioritiza- tion tools for phenotypes which are not related with diseases generally or diseases with which no genes have yet been associated in particular. Chromatin immunoprecipitation followed by next generation sequencing (ChIP-Seq) is a method of choice to study the gene regulation processes responsible for the expression of cellular phenotypes. Among publicly available computational pipelines for the processing of ChIP-Seq data, there is a lack of tools for the downstream analysis of composite motifs and preferred binding distances of the DNA binding proteins.
    [Show full text]
  • Identification of Genes Involved in Low Aminoglycoside-Induced SOS Response in Vibrio Cholerae: a Role for Transcription Stalling and Mfd Helicase
    Identification of genes involved in low aminoglycoside-induced SOS response in Vibrio cholerae: a role for transcription stalling and Mfd helicase. Z. Baharoglu, A. Babosan, D. Mazel To cite this version: Z. Baharoglu, A. Babosan, D. Mazel. Identification of genes involved in low aminoglycoside-induced SOS response in Vibrio cholerae: a role for transcription stalling and Mfd helicase.. Nucleic Acids Research, Oxford University Press, 2014, 42 (4), pp.2366-2379. 10.1093/nar/gkt1259. pasteur- 01423602 HAL Id: pasteur-01423602 https://hal-pasteur.archives-ouvertes.fr/pasteur-01423602 Submitted on 30 Dec 2016 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License 2366–2379 Nucleic Acids Research, 2014, Vol. 42, No. 4 Published online 6 December 2013 doi:10.1093/nar/gkt1259 Identification of genes involved in low aminoglycoside-induced SOS response in Vibrio cholerae: a role for transcription stalling and Mfd helicase Zeynep Baharoglu1,2,*, Anamaria Babosan1,2 and Didier Mazel1,2,*
    [Show full text]
  • Indoxyl Sulfate and P-Cresyl Sulfate Promote Vascular Calcification and Associate with Glucose Intolerance
    BASIC RESEARCH www.jasn.org Indoxyl Sulfate and p-Cresyl Sulfate Promote Vascular Calcification and Associate with Glucose Intolerance Britt Opdebeeck ,1 Stuart Maudsley,2,3 Abdelkrim Azmi,3 Annelies De Maré,1 Wout De Leger,4 Bjorn Meijers,5,6 Anja Verhulst,1 Pieter Evenepoel,5,6 Patrick C. D’Haese,1 and Ellen Neven1 1Laboratory of Pathophysiology, Department of Biomedical Sciences, 2Receptor Biology Lab, Department of Biomedical Sciences, and 3Translational Neurobiology Group, Flanders Institute of Biotechnology Center for Molecular Neurology, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; 4Division of Molecular Design and Synthesis, Department of Chemistry and 6Laboratory of Nephrology, Department of Immunology and Microbiology, Catholic University of Leuven, Leuven, Belgium; and 5Division of Internal Medicine, Nephrology, University Hospitals Leuven, Leuven, Belgium ABSTRACT Background Protein-bound uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (PCS) have been associ- ated with cardiovascular morbidity and mortality in patients with CKD. However, direct evidence for a role of these toxins in CKD-related vascular calcification has not been reported. Methods To study early and late vascular alterations by toxin exposure, we exposed CKD rats to vehicle, IS (150 mg/kg per day), or PCS (150 mg/kg per day) for either 4 days (short-term exposure) or 7 weeks (long-term exposure). We also performed unbiased proteomic analyses of arterial samples coupled to functional bioinformatic annotation analyses to investigate molecular signaling events associated with toxin-mediated arterial calcification. Results Long-term exposure to either toxin at serum levels similar to those experienced by patients with CKD significantly increased calcification in the aorta and peripheral arteries.
    [Show full text]
  • Rabbit Anti-ENY2 Antibody-SL14605R
    SunLong Biotech Co.,LTD Tel: 0086-571- 56623320 Fax:0086-571- 56623318 E-mail:[email protected] www.sunlongbiotech.com Rabbit Anti-ENY2 antibody SL14605R Product Name: ENY2 Chinese Name: ENY2蛋白抗体 1810057B09Rik; 6720481I12; DC6; e(y)2; Enhancer of yellow 2 transcription factor Alias: homolog; eny2; ENY2_HUMAN; Ey2. Organism Species: Rabbit Clonality: Polyclonal React Species: Human,Mouse,Rat,Chicken,Dog,Pig,Cow,Horse,Rabbit,Sheep,Rhesus monkey ELISA=1:500-1000IHC-P=1:400-800IHC-F=1:400-800ICC=1:100-500IF=1:100- 500（Paraffin sections need antigen repair） Applications: not yet tested in other applications. optimal dilutions/concentrations should be determined by the end user. Molecular weight: 12kDa Cellular localization: The nucleus Form: Lyophilized or Liquid Concentration: 1mg/ml immunogen: KLH conjugated synthetic peptide derived from human ENY2:51-101/101 Lsotype: IgGwww.sunlongbiotech.com Purification: affinity purified by Protein A Storage Buffer: 0.01M TBS(pH7.4) with 1% BSA, 0.03% Proclin300 and 50% Glycerol. Store at -20 °C for one year. Avoid repeated freeze/thaw cycles. The lyophilized antibody is stable at room temperature for at least one month and for greater than a year Storage: when kept at -20°C. When reconstituted in sterile pH 7.4 0.01M PBS or diluent of antibody the antibody is stable for at least two weeks at 2-4 °C. PubMed: PubMed Made up of nearly 146 million bases, chromosome 8 encodes about 800 genes. Translocation of portions of chromosome 8 with amplifications of the c-Myc gene are found in some leukemias and lymphomas, and typically associated with a poor Product Detail: prognosis.
    [Show full text]
  • Content Based Search in Gene Expression Databases and a Meta-Analysis of Host Responses to Infection
    Content Based Search in Gene Expression Databases and a Meta-analysis of Host Responses to Infection A Thesis Submitted to the Faculty of Drexel University by Francis X. Bell in partial fulfillment of the requirements for the degree of Doctor of Philosophy November 2015 c Copyright 2015 Francis X. Bell. All Rights Reserved. ii Acknowledgments I would like to acknowledge and thank my advisor, Dr. Ahmet Sacan. Without his advice, support, and patience I would not have been able to accomplish all that I have. I would also like to thank my committee members and the Biomed Faculty that have guided me. I would like to give a special thanks for the members of the bioinformatics lab, in particular the members of the Sacan lab: Rehman Qureshi, Daisy Heng Yang, April Chunyu Zhao, and Yiqian Zhou. Thank you for creating a pleasant and friendly environment in the lab. I give the members of my family my sincerest gratitude for all that they have done for me. I cannot begin to repay my parents for their sacrifices. I am eternally grateful for everything they have done. The support of my sisters and their encouragement gave me the strength to persevere to the end. iii Table of Contents LIST OF TABLES.......................................................................... vii LIST OF FIGURES ........................................................................ xiv ABSTRACT ................................................................................ xvii 1. A BRIEF INTRODUCTION TO GENE EXPRESSION............................. 1 1.1 Central Dogma of Molecular Biology........................................... 1 1.1.1 Basic Transfers .......................................................... 1 1.1.2 Uncommon Transfers ................................................... 3 1.2 Gene Expression ................................................................. 4 1.2.1 Estimating Gene Expression ............................................ 4 1.2.2 DNA Microarrays ......................................................
    [Show full text]
  • Role of the Escherichia Coli Recq DNA Helicase in SOS Signaling and Genome Stabilization at Stalled Replication Forks
    Downloaded from genesdev.cshlp.org on September 25, 2021 - Published by Cold Spring Harbor Laboratory Press Role of the Escherichia coli RecQ DNA helicase in SOS signaling and genome stabilization at stalled replication forks Takashi Hishida,1,5,7 Yong-Woon Han,1,5,6 Tatsuya Shibata,1 Yoshino Kubota,1 Yoshizumi Ishino,3 Hiroshi Iwasaki,4 and Hideo Shinagawa1,2,8 1Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan; 2CREST, Japan Science and Technology Agency, Osaka 565-0871, Japan; 3Department of Genetic Resources Technology, Faculty of Agriculture, Kyushu University, Fukuoka, 812-8581, Japan; 4Graduate School of Integrated Science, Yokohama City University, Yokohama, 230-0045 Japan The RecQ protein family is a highly conserved group of DNA helicases that play roles in maintaining genomic stability. In this study, we present biochemical and genetic evidence that Escherichia coli RecQ processes stalled replication forks and participates in SOS signaling. Cells that carry dnaE486, a mutation in the DNA polymerase III ␣-catalytic subunit, induce an RecA-dependent SOS response and become highly filamented at the semirestrictive temperature (38°C). An recQ mutation suppresses the induction of SOS response and the filamentation in the dnaE486 mutant at 38°C, causing appearance of a high proportion of anucleate cells. In vitro, RecQ binds and unwinds forked DNA substrates with a gap on the leading strand more efficiently than those with a gap on the lagging strand or Holliday junction DNA. RecQ unwinds the template duplex ahead of the fork, and then the lagging strand is unwound. Consequently, this process generates a single-stranded DNA (ssDNA) gap on the lagging strand adjacent to a replication fork.
    [Show full text]