Dnag Primase—A Target for the Development of Novel Antibacterial Agents
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Analysis of a Multicomponent Thermostable DNA Polymerase III Replicase from an Extreme Thermophile*
THE JOURNAL OF BIOLOGICAL CHEMISTRY Vol. 277, No. 19, Issue of May 10, pp. 17334–17348, 2002 © 2002 by The American Society for Biochemistry and Molecular Biology, Inc. Printed in U.S.A. Analysis of a Multicomponent Thermostable DNA Polymerase III Replicase from an Extreme Thermophile* Received for publication, October 23, 2001, and in revised form, February 18, 2002 Published, JBC Papers in Press, February 21, 2002, DOI 10.1074/jbc.M110198200 Irina Bruck‡, Alexander Yuzhakov§¶, Olga Yurieva§, David Jeruzalmi§, Maija Skangalis‡§, John Kuriyan‡§, and Mike O’Donnell‡§ʈ From §The Rockefeller University and ‡Howard Hughes Medical Institute, New York, New York 10021 This report takes a proteomic/genomic approach to polymerase III (pol III) structure and function has been ob- characterize the DNA polymerase III replication appa- tained from studies of the Escherichia coli replicase, DNA ratus of the extreme thermophile, Aquifex aeolicus. polymerase III holoenzyme (reviewed in Ref. 6). Therefore, a Genes (dnaX, holA, and holB) encoding the subunits re- brief overview of its structure and function is instructive for the ␦ ␦ quired for clamp loading activity ( , , and ) were iden- comparisons to be made in this report. In E. coli, the catalytic Downloaded from tified. The dnaX gene produces only the full-length subunit of DNA polymerase III is the ␣ subunit (129.9 kDa) product, , and therefore differs from Escherichia coli encoded by dnaE; it lacks a proofreading exonuclease (7). The dnaX that produces two proteins (␥ and ). Nonetheless, Ј Ј ⑀ ␦␦ proofreading 3 –5 -exonuclease activity is contained in the the A. aeolicus proteins form a complex. The dnaN ␣ ,␦␦ (27.5 kDa) subunit (dnaQ) that forms a 1:1 complex with (8  gene encoding the clamp was identified, and the ␣Ϫ⑀  9). -
DNA POLYMERASE III HOLOENZYME: Structure and Function of a Chromosomal Replicating Machine
Annu. Rev. Biochem. 1995.64:171-200 Copyright Ii) 1995 byAnnual Reviews Inc. All rights reserved DNA POLYMERASE III HOLOENZYME: Structure and Function of a Chromosomal Replicating Machine Zvi Kelman and Mike O'Donnell} Microbiology Department and Hearst Research Foundation. Cornell University Medical College. 1300York Avenue. New York. NY }0021 KEY WORDS: DNA replication. multis ubuni t complexes. protein-DNA interaction. DNA-de penden t ATPase . DNA sliding clamps CONTENTS INTRODUCTION........................................................ 172 THE HOLO EN ZYM E PARTICL E. .......................................... 173 THE CORE POLYMERASE ............................................... 175 THE � DNA SLIDING CLAM P............... ... ......... .................. 176 THE yC OMPLEX MATCHMAKER......................................... 179 Role of ATP . .... .............. ...... ......... ..... ............ ... 179 Interaction of y Complex with SSB Protein .................. ............... 181 Meclwnism of the yComplex Clamp Loader ................................ 181 Access provided by Rockefeller University on 08/07/15. For personal use only. THE 't SUBUNIT . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. 182 Annu. Rev. Biochem. 1995.64:171-200. Downloaded from www.annualreviews.org AS YMMETRIC STRUC TURE OF HOLO EN ZYM E . 182 DNA PO LYM ER AS E III HOLO ENZ YME AS A REPLIC ATING MACHINE ....... 186 Exclwnge of � from yComplex to Core .................................... 186 Cycling of Holoenzyme on the LaggingStrand -
Distinct Co-Evolution Patterns of Genes Associated to DNA Polymerase III Dnae and Polc Stefan Engelen1,2, David Vallenet2, Claudine Médigue2 and Antoine Danchin1,3*
Engelen et al. BMC Genomics 2012, 13:69 http://www.biomedcentral.com/1471-2164/13/69 RESEARCHARTICLE Open Access Distinct co-evolution patterns of genes associated to DNA polymerase III DnaE and PolC Stefan Engelen1,2, David Vallenet2, Claudine Médigue2 and Antoine Danchin1,3* Abstract Background: Bacterial genomes displaying a strong bias between the leading and the lagging strand of DNA replication encode two DNA polymerases III, DnaE and PolC, rather than a single one. Replication is a highly unsymmetrical process, and the presence of two polymerases is therefore not unexpected. Using comparative genomics, we explored whether other processes have evolved in parallel with each polymerase. Results: Extending previous in silico heuristics for the analysis of gene co-evolution, we analyzed the function of genes clustering with dnaE and polC. Clusters were highly informative. DnaE co-evolves with the ribosome, the transcription machinery, the core of intermediary metabolism enzymes. It is also connected to the energy-saving enzyme necessary for RNA degradation, polynucleotide phosphorylase. Most of the proteins of this co-evolving set belong to the persistent set in bacterial proteomes, that is fairly ubiquitously distributed. In contrast, PolC co- evolves with RNA degradation enzymes that are present only in the A+T-rich Firmicutes clade, suggesting at least two origins for the degradosome. Conclusion: DNA replication involves two machineries, DnaE and PolC. DnaE co-evolves with the core functions of bacterial life. In contrast PolC co-evolves with a set of RNA degradation enzymes that does not derive from the degradosome identified in gamma-Proteobacteria. This suggests that at least two independent RNA degradation pathways existed in the progenote community at the end of the RNA genome world. -
Glycolytic Pyruvate Kinase Moonlighting Activities in DNA Replication
Glycolytic pyruvate kinase moonlighting activities in DNA replication initiation and elongation Steff Horemans, Matthaios Pitoulias, Alexandria Holland, Panos Soultanas, Laurent Janniere To cite this version: Steff Horemans, Matthaios Pitoulias, Alexandria Holland, Panos Soultanas, Laurent Janniere. Gly- colytic pyruvate kinase moonlighting activities in DNA replication initiation and elongation. 2020. hal-02992157 HAL Id: hal-02992157 https://hal.archives-ouvertes.fr/hal-02992157 Preprint submitted on 10 Dec 2020 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. Glycolytic pyruvate kinase moonlighting activities in DNA replication initiation and elongation Steff Horemans1, Matthaios Pitoulias2, Alexandria Holland2, Panos Soultanas2¶ and Laurent Janniere1¶ 1 : Génomique Métabolique, Genoscope, Institut François Jacob, CEA, CNRS, Univ Evry, Université Paris-Saclay, 91057 Evry, France 2 : Biodiscovery Institute, School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, UK Short title: PykA moonlighting activity in DNA replication Key Words: DNA replication; replication control; central carbon metabolism; glycolytic enzymes; replication enzymes; cell cycle; allosteric regulation. ¶ : Corresponding authors Laurent Janniere: [email protected] Panos Soultanas : [email protected] 1 SUMMARY Cells have evolved a metabolic control of DNA replication to respond to a wide range of nutritional conditions. -
Coordination Between Nucleotide Excision Repair And
RESEARCH ARTICLE Coordination between nucleotide excision repair and specialized polymerase DnaE2 action enables DNA damage survival in non-replicating bacteria Asha Mary Joseph1, Saheli Daw1, Ismath Sadhir1,2, Anjana Badrinarayanan1* 1National Centre for Biological Sciences - Tata Institute of Fundamental Research, Bangalore, India; 2Max Planck Institute for Terrestrial Microbiology, LOEWE Centre for Synthetic Microbiology (SYNMIKRO), Marburg, Germany Abstract Translesion synthesis (TLS) is a highly conserved mutagenic DNA lesion tolerance pathway, which employs specialized, low-fidelity DNA polymerases to synthesize across lesions. Current models suggest that activity of these polymerases is predominantly associated with ongoing replication, functioning either at or behind the replication fork. Here we provide evidence for DNA damage-dependent function of a specialized polymerase, DnaE2, in replication- independent conditions. We develop an assay to follow lesion repair in non-replicating Caulobacter and observe that components of the replication machinery localize on DNA in response to damage. These localizations persist in the absence of DnaE2 or if catalytic activity of this polymerase is mutated. Single-stranded DNA gaps for SSB binding and low-fidelity polymerase-mediated synthesis are generated by nucleotide excision repair (NER), as replisome components fail to localize in the absence of NER. This mechanism of gap-filling facilitates cell cycle restoration when cells are released into replication-permissive conditions. Thus, such cross-talk (between activity of NER and specialized polymerases in subsequent gap-filling) helps preserve genome integrity and enhances survival in a replication-independent manner. *For correspondence: [email protected] Introduction Competing interests: The DNA damage is a threat to genome integrity and can lead to perturbations to processes of replica- authors declare that no tion and transcription. -
Coordination Between Nucleotide Excision Repair and Specialized Polymerase Dnae2 Action 2 Enables DNA Damage Survival in Non-Replicating Bacteria
bioRxiv preprint doi: https://doi.org/10.1101/2021.02.15.431208; this version posted February 15, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Coordination between nucleotide excision repair and specialized polymerase DnaE2 action 2 enables DNA damage survival in non-replicating bacteria 3 4 5 6 7 Asha Mary Joseph, Saheli Daw, Ismath Sadhir and Anjana Badrinarayanan* 8 9 National Centre for Biological Sciences - Tata Institute of Fundamental Research, Bellary Road, 10 Bangalore 560065, Karnataka, India, Phone: 91 80 23666547 11 *Correspondence to: [email protected] 12 13 Keywords 14 Caulobacter crescentus, DnaE2, DNA repair, error-prone polymerases, non-replicating cells, 15 nucleotide excision repair, single-cell imaging, fluorescence microscopy 16 17 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.02.15.431208; this version posted February 15, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 18 Abstract 19 Translesion synthesis (TLS) is a highly conserved mutagenic DNA lesion tolerance pathway, which 20 employs specialized, low-fidelity DNA polymerases to synthesize across lesions. Current models 21 suggest that activity of these polymerases is predominantly associated with ongoing replication, 22 functioning either at or behind the replication fork. -
(12) United States Patent (10) Patent No.: US 6,555,349 B1 O'donnell (45) Date of Patent: Apr
USOO6555349B1 (12) United States Patent (10) Patent No.: US 6,555,349 B1 O'Donnell (45) Date of Patent: Apr. 29, 2003 (54) METHODS FOR AMPLIFYING AND Xiao et al., “DNA Polymerase III Accessory Proteins. III. SEQUENCING NUCLEIC ACID MOLECULES HolC and holD Encoding X and up,” J. Biol. Chem. USING ATHREE COMPONENT 268: 11779–84 (1993). POLYMERASE Xiao et al., “DNA Polymerase III Accessory Proteins. IV. Characterization of X and up,” J. Biol. Chem. 268: 11773-78 (75) Inventor: Michael E. O'Donnell, (1993). Hastings-on-Hudson, NY (US) Studwell-Vaughan et al., “DNA Polymerase III Accessory (73) Assignees: Cornell Research Foundation, Inc., Proteins. V. 0 Encoded by holE,” J. Biol. Chem. Ithaca, NY (US); The Rockefeller 268:11785-91 (1993). University, New York, NY (US) Carter et al., “Molecular Cloning, Sequencing, and Overex pression of the Structural Gene Encoding the Ó Subunit of E. (*) Notice: Subject to any disclaimer, the term of this Coli DNA Polymerase III Holoenzyme,” J. Bacteriol. patent is extended or adjusted under 35 174:7013-25 (1993). U.S.C. 154(b) by 0 days. Carter et al., “Identification, Isolation, and Characterization of the Structural Gene Encoding the ÖN Subunit of E. Coli DNA Polymerase III Holoenzyme,” J. Bacteriol, (21) Appl. No.: 09/325,067 175:3812–22 (1993). Carter et al., “Isolation, Sequencing, and Overexpression of (22) Filed: Jun. 3, 1999 the Gene Encoding the 0 Subunit of DNA Polymerase III Related U.S. Application Data Holoenzyme,” Nuc. Acids Res. 21:3281–86 (1993). Carter et al., “Identification, Isolation, and Overexpression (63) Continuation-in-part of application No. -
Proposal for a Minimal DNA Auto-Replicative System
Chapter 5 Proposal for a Minimal DNA Auto-Replicative System Agustino Martinez-Antonio, Laura Espindola-Serna and Cesar Quiñones-Valles Additional information is available at the end of the chapter http://dx.doi.org/10.5772/51986 1. Introduction DNA replication allows cell division and population growth of living organisms. Here we will focus on DNA replication in prokaryotic single celled microorganisms. Several excellent reviews of the molecular processes that carry out DNA replication in bacteria already exist, E. coli being the model described in most detail (Langston LD et al., 2009; Quiñones-Valles et al., 2011). Briefly, the process begins when DnaA (DNA initiator replication protein) in its activated form (DnaA-ATP) recognizes and binds the oriC (origin of replication on the bacte‐ rial chromosome). In the following step, the replisome is assembled and binds to the com‐ plex of DnaA-ATP at the oriC. Next, the DNA strands are separated and synthesis of the complementary strands initiates followed by elongation steps. The molecular mechanisms of elongation differ depending on the strand used as a template; the leading strand is repli‐ cated continuously starting from a unique RNA primer, whereas on the lagging strand DNA polymerase III must recognize several RNA primers, previously synthesized by DnaG, and then replicate each DNA fragment (Okazaki fragments). This is followed by the replacement of RNA primers by DNA polymerase I, and removal of nicks by a DNA ligase. The whole process concludes when replisomes reach the ter site, almost opposite to oriC on the circular DNA molecule. Tus proteins are attached to the ter sites and when replisomes reach these complexes, they collide and finally are disassembled (see Figure 1 for an overview of the whole process). -
1.1 DNA Polymerase III Holoenzyme
Mechanisms of E. coli DNA polymerase III and polymerase management by UmuD during DNA replication by David A. Murison B.S. in Chemistry, Trinity College to The Faculty of The College of Science of Northeastern University in partial fulfillment of the requirements for the degree of Doctor of Philosophy March 24, 2017 Dissertation directed by Penny J. Beuning Associate Professor of Chemistry and Chemical Biology Acknowledgements I would like to thank my graduate advisor, Dr. Penny J. Beuning, for allowing me to work in her lab. I have learned nearly everything that I know about molecular biology and cell culture while under her guidance, and I thank her tremendously for her patience and support while learning many new techniques. I could not ask for a better scientific role model than Penny, and her dedication to sound-science will serve as a paragon in my future work. To my mother and father, Susan C. Wagner and David R. Murison, I cannot put into words my gratitude and appreciation for all of the love, support, and encouragement you’ve given me as your son. Thank you for allowing me the opportunity to get the best education possible at every stage of my life. I love you both dearly, and I feel blessed to be your son. I would like to thank my thesis committee members: Dr. David E. Budil, Dr. Mary Jo Ondrechen, and Dr. Mark C. Williams. Thank you for accepting my invitation to be on my committee, and I am grateful for the advisory and guidance each have provided during committee meetings and in review of my dissertation. -
Architecture and Conservation of the Bacterial DNA Replication Machinery, an Underexploited Drug Target
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Research Online University of Wollongong Research Online Faculty of Science - Papers (Archive) Faculty of Science, Medicine and Health 2012 Architecture and conservation of the bacterial DNA replication machinery, an underexploited drug target Andrew Robinson University of Wollongong, [email protected] Rebecca J. Causer University of Wollongong, [email protected] Nicholas E. Dixon University of Wollongong, [email protected] Follow this and additional works at: https://ro.uow.edu.au/scipapers Part of the Life Sciences Commons, Physical Sciences and Mathematics Commons, and the Social and Behavioral Sciences Commons Recommended Citation Robinson, Andrew; Causer, Rebecca J.; and Dixon, Nicholas E.: Architecture and conservation of the bacterial DNA replication machinery, an underexploited drug target 2012, 352-372. https://ro.uow.edu.au/scipapers/2996 Research Online is the open access institutional repository for the University of Wollongong. For further information contact the UOW Library: [email protected] Architecture and conservation of the bacterial DNA replication machinery, an underexploited drug target Abstract "New antibiotics with novel modes of action are required to combat the growing threat posed by multi- drug resistant bacteria. Over the last decade, genome sequencing and other high-throughput techniques have provided tremendous insight into the molecular processes underlying cellular functions in a wide range of bacterial species. We can now use these data to assess the degree of conservation of certain aspects of bacterial physiology, to help choose the best cellular targets for development of new broad- spectrum antibacterials. -
Architecture and Conservation of the Bacterial DNA Replication Machinery, an Underexploited Drug Target
352 Current Drug Targets, 2012, 13, 352-372 Architecture and Conservation of the Bacterial DNA Replication Machinery, an Underexploited Drug Target Andrew Robinson, Rebecca J. Causer and Nicholas E. Dixon* School of Chemistry, University of Wollongong, Australia Abstract: New antibiotics with novel modes of action are required to combat the growing threat posed by multi-drug resistant bacteria. Over the last decade, genome sequencing and other high-throughput techniques have provided tremendous insight into the molecular processes underlying cellular functions in a wide range of bacterial species. We can now use these data to assess the degree of conservation of certain aspects of bacterial physiology, to help choose the best cellular targets for development of new broad-spectrum antibacterials. DNA replication is a conserved and essential process, and the large number of proteins that interact to replicate DNA in bacteria are distinct from those in eukaryotes and archaea; yet none of the antibiotics in current clinical use acts directly on the replication machinery. Bacterial DNA synthesis thus appears to be an underexploited drug target. However, before this system can be targeted for drug design, it is important to understand which parts are conserved and which are not, as this will have implications for the spectrum of activity of any new inhibitors against bacterial species, as well as the potential for development of drug resistance. In this review we assess similarities and differences in replication components and mechanisms across the bacteria, highlight current progress towards the discovery of novel replication inhibitors, and suggest those aspects of the replication machinery that have the greatest potential as drug targets. -
The Topoisomerase IV Parc Subunit Colocalizes with the Caulobacter Replisome and Is Required for Polar Localization of Replication Origins
The topoisomerase IV ParC subunit colocalizes with the Caulobacter replisome and is required for polar localization of replication origins Sherry C. Wang*† and Lucy Shapiro*‡ *Department of Developmental Biology, Stanford University School of Medicine, Beckman Center B300, 279 Campus Drive, Stanford, CA 94305; and †Cancer Biology Program, Stanford Medical School, Stanford, CA 94305 Contributed by Lucy Shapiro, April 9, 2004 The process of bacterial DNA replication generates chromosomal motile swarmer cell and a stalked cell (Fig. 1A). In the swarmer topological constraints that are further confounded by simulta- cell, which is unable to initiate DNA replication, the origin of neous transcription. Topoisomerases play a key role in ensuring replication is located at the flagellated pole (1). DNA replication orderly replication and partition of DNA in the face of a continu- initiates when the swarmer cell differentiates into a stalked cell ously changing DNA tertiary structure. In addition to topological and replisome components assemble onto the replication origin constraints, the cellular position of the replication origin is strictly at the stalked cell pole (14). A copy of the replicated origin controlled during the cell cycle. In Caulobacter crescentus, the moves rapidly to the pole opposite the stalk in what is thought origin of DNA replication is located at the cell pole. Upon initiation to be an active process [see the companion article by Viollier et of DNA replication, one copy of the duplicated origin sequence al. (15) in this issue of PNAS], and as DNA replication proceeds, rapidly appears at the opposite cell pole. To determine whether the the replisome progresses from the stalked pole to the division maintenance of DNA topology contributes to the dynamic posi- plane (14).