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https://www.readbyqxmd.com/read/29290468/stabilization-of-reversed-replication-forks-by-telomerase-drives-telomere-catastrophe
#1
Pol Margalef, Panagiotis Kotsantis, Valerie Borel, Roberto Bellelli, Stephanie Panier, Simon J Boulton
Telomere maintenance critically depends on the distinct activities of telomerase, which adds telomeric repeats to solve the end replication problem, and RTEL1, which dismantles DNA secondary structures at telomeres to facilitate replisome progression. Here, we establish that reversed replication forks are a pathological substrate for telomerase and the source of telomere catastrophe in Rtel1-/- cells. Inhibiting telomerase recruitment to telomeres, but not its activity, or blocking replication fork reversal through PARP1 inhibition or depleting UBC13 or ZRANB3 prevents the rapid accumulation of dysfunctional telomeres in RTEL1-deficient cells...
December 27, 2017: Cell
https://www.readbyqxmd.com/read/29234005/proteomic-analyses-identify-arh3-as-a-serine-mono-adp-ribosylhydrolase
#2
Jeannette Abplanalp, Mario Leutert, Emilie Frugier, Kathrin Nowak, Roxane Feurer, Jiro Kato, Hans V A Kistemaker, Dmitri V Filippov, Joel Moss, Amedeo Caflisch, Michael O Hottiger
ADP-ribosylation is a posttranslational modification that exists in monomeric and polymeric forms. Whereas the writers (e.g. ARTD1/PARP1) and erasers (e.g. PARG, ARH3) of poly-ADP-ribosylation (PARylation) are relatively well described, the enzymes involved in mono-ADP-ribosylation (MARylation) have been less well investigated. While erasers for the MARylation of glutamate/aspartate and arginine have been identified, the respective enzymes with specificity for serine were missing. Here we report that, in vitro, ARH3 specifically binds and demodifies proteins and peptides that are MARylated...
December 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29205912/adp-ribosylation-of-dna-moving-into-focus
#3
Christian Dölle, Mathias Ziegler
In this issue of The FEBS Journal, Munnur and Ahel describe the reversible mono-ADP-ribosylation of DNA by PARP3, a member of the poly-ADP-ribose-polymerase family known to modify proteins. They demonstrate a selective ADP-ribosylation of the 5'-phosphate group on DNA ends and show that the modification can be reversed by several known ADP-ribosylhydrolases including PARG.
December 2017: FEBS Journal
https://www.readbyqxmd.com/read/29179156/radiosensitization-with-an-inhibitor-of-poly-adp-ribose-glycohydrolase-a-comparison-with-the-parp1-2-3-inhibitor-olaparib
#4
Polly Gravells, James Neale, Emma Grant, Amit Nathubhai, Kate M Smith, Dominic I James, Helen E Bryant
Upon DNA binding the poly(ADP-ribose) polymerase family of enzymes (PARPs) add multiple ADP-ribose subunits to themselves and other acceptor proteins. Inhibitors of PARPs have become an exciting and real prospect for monotherapy and as sensitizers to ionising radiation (IR). The action of PARPs are reversed by poly(ADP-ribose) glycohydrolase (PARG). Until recently studies of PARG have been limited by the lack of an inhibitor. Here, a first in class, specific, and cell permeable PARG inhibitor, PDD00017273, is shown to radiosensitize...
November 22, 2017: DNA Repair
https://www.readbyqxmd.com/read/29175125/changes-in-tetracycline-partitioning-and-bacteria-phage-comediated-args-in-microplastic-contaminated-greenhouse-soil-facilitated-by-sophorolipid
#5
Mingming Sun, Mao Ye, Wentao Jiao, Yanfang Feng, Pingfeng Yu, Manqiang Liu, Jiaguo Jiao, Xiaojia He, Kuan Liu, Yuanchao Zhao, Jun Wu, Xin Jiang, Feng Hu
The emerging mixed contamination of antibiotics and microplastics in greenhouse soil has made the control of antibiotic resistant gene (ARG) transmission a novel challenge. In this work, surfactant sophorolipid was applied to enhance the dissipation of tetracycline (TC) and tet genes in the presence of microplastics in greenhouse soil. During 49days of incubation, soil bacteria and phages were both found to be the crucial reservoirs of ARGs. Meanwhile, microplastic's presence significantly inhibited the dissipation of TC and ARGs in the soil...
November 21, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/29058706/histidine-kinases-and-the-missing-phosphoproteome-from-prokaryotes-to-eukaryotes
#6
Kevin Adam, Tony Hunter
Protein phosphorylation is the most common type of post-translational modification in eukaryotes. The phosphoproteome is defined as the complete set of experimentally detectable phosphorylation sites present in a cell's proteome under various conditions. However, we are still far from identifying all the phosphorylation sites in a cell mainly due to the lack of information about phosphorylation events involving residues other than Ser, Thr and Tyr. Four types of phosphate-protein linkage exist and these generate nine different phosphoresidues-pSer, pThr, pTyr, pHis, pLys, pArg, pAsp, pGlu and pCys...
October 23, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29054115/reversible-mono-adp-ribosylation-of-dna-breaks
#7
Deeksha Munnur, Ivan Ahel
ADP-ribosylation is a chemical modification of macromolecules that plays an important role in regulation of quintessential biological processes such as DNA repair, transcription, chromatin remodelling, stress response, apoptosis, bacterial metabolism and many others. ADP-ribosylation is carried out by ADP-ribosyltransferase proteins, such as poly(ADP-ribose) polymerases (PARPs) that transfer either monomer or polymers of ADP-ribose onto the molecular targets by using nicotinamide adenine dinucleotide (NAD(+) ) as a cofactor...
October 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28956188/biochemical-and-genetic-analysis-of-a-unique-poly-adp-ribosyl-glycohydrolase-parg-of-the-pathogenic-fungus-fusarium-oxysporum-f-sp-lycopersici
#8
Carlos A Araiza-Cervantes, Víctor Meza-Carmen, Guadalupe Martínez-Cadena, M Isabel G Roncero, Georgina E Reyna-López, Bernardo Franco
The genome sequence of the plant pathogen Fusarium oxysporum f. sp. lycopersici contains a single gene encoding a predicted poly(ADP-ribose) glycohydrolase (FOXG_05947.2, PARG). Here, we assessed whether this gene has a role as a global regulator of DNA repair or in virulence as an ADP ribosylating toxin homologue of bacteria. The PARG protein was purified after expressing its encoding gene in Escherichia coli. Its inhibition by 6,9-diamino-2-ethoxyacridine lactate monohydrate and tannins was similar to its human orthologue that is involved in DNA repair...
September 27, 2017: Antonie Van Leeuwenhoek
https://www.readbyqxmd.com/read/28934471/a-novel-non-canonical-pip-box-mediates-parg-interaction-with-pcna
#9
Tanja Kaufmann, Irina Grishkovskaya, Anton A Polyansky, Sebastian Kostrhon, Eva Kukolj, Karin M Olek, Sebastien Herbert, Etienne Beltzung, Karl Mechtler, Thomas Peterbauer, Josef Gotzmann, Lijuan Zhang, Markus Hartl, Bojan Zagrovic, Kareem Elsayad, Kristina Djinovic-Carugo, Dea Slade
Poly(ADP-ribose) glycohydrolase (PARG) regulates cellular poly(ADP-ribose) (PAR) levels by rapidly cleaving glycosidic bonds between ADP-ribose units. PARG interacts with proliferating cell nuclear antigen (PCNA) and is strongly recruited to DNA damage sites in a PAR- and PCNA-dependent fashion. Here we identified PARG acetylation site K409 that is essential for its interaction with PCNA, its localization within replication foci and its recruitment to DNA damage sites. We found K409 to be part of a non-canonical PIP-box within the PARG disordered regulatory region...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28723107/chemical-approaches-to-investigate-labile-peptide-and-protein-phosphorylation
#10
Anett Hauser, Martin Penkert, Christian P R Hackenberger
Protein phosphorylation is by far the most abundant and most studied post-translational modification (PTM). For a long time, phosphate monoesters of serine (pSer), threonine (pThr), and tyrosine (pTyr) have been considered as the only relevant forms of phosphorylation in organisms. Recently, several research groups have dedicated their efforts to the investigation of other, less characterized phosphoamino acids as naturally occurring PTMs. Such apparent peculiar phosphorylations include the phosphoramidates of histidine (pHis), arginine (pArg), and lysine (pLys), the phosphorothioate of cysteine (pCys), and the anhydrides of pyrophosphorylated serine (ppSer) and threonine (ppThr)...
July 19, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28695524/studying-catabolism-of-protein-adp-ribosylation
#11
Luca Palazzo, Dominic I James, Ian D Waddell, Ivan Ahel
Protein ADP-ribosylation is a conserved posttranslational modification that regulates many major cellular functions, such as DNA repair, transcription, translation, signal transduction, stress response, cell division, aging, and cell death. Protein ADP-ribosyl transferases catalyze the transfer of an ADP-ribose (ADPr) group from the β-nicotinamide adenine dinucleotide (β-NAD(+)) cofactor onto a specific target protein with the subsequent release of nicotinamide. ADP-ribosylation leads to changes in protein structure, function, stability, and localization, thus defining the appropriate cellular response...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28695523/purification-of-recombinant-human-parg-and-activity-assays
#12
Jean-Christophe Amé, Éléa Héberlé, Barbara Camuzeaux, Françoise Dantzer, Valérie Schreiber
The purification of Poly(ADP-ribose) glycohydrolase (PARG) from overexpressing bacteria Escherichia coli is described here to a fast and reproducible one chromatographic step protocol. After cell lysis, GST-PARG-fusion proteins from the crude extract are affinity purified by a Glutathione 4B Sepharose chromatographic step. The PARG proteins are then freed from their GST-fusion by overnight enzymatic cleavage using the preScission protease. As described in the protocol, more than 500 μg of highly active human PARG can be obtained from 1...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28695503/cell-cycle-resolved-measurements-of-poly-adp-ribose-formation-and-dna-damage-signaling-by-quantitative-image-based-cytometry
#13
Jone Michelena, Matthias Altmeyer
Formation of poly(ADP-ribose) (PAR) marks intracellular stress signaling and is notably induced upon DNA damage. PAR polymerases (PARPs) catalyze PAR synthesis upon genotoxic stress and thereby recruit multiple proteins to damaged chromatin. PAR induction is transient and antagonized by the action of PAR glycohydrolase (PARG). Given that poly(ADP-ribosyl)ation (PARylation) is involved in genome integrity maintenance and other vital cellular functions, but also in light of the recent approval of PARP inhibitors for cancer treatments, reliable measurements of intracellular PAR formation have gained importance...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28687616/posttranscriptional-regulation-of-parg-mrna-by-hur-facilitates-dna-repair-and-resistance-to-parp-inhibitors
#14
Saswati N Chand, Mahsa Zarei, Matthew J Schiewer, Akshay R Kamath, Carmella Romeo, Shruti Lal, Joseph A Cozzitorto, Avinoam Nevler, Laura Scolaro, Eric Londin, Wei Jiang, Nicole Meisner-Kober, Michael J Pishvaian, Karen E Knudsen, Charles J Yeo, John M Pascal, Jordan M Winter, Jonathan R Brody
The majority of pancreatic ductal adenocarcinomas (PDAC) rely on the mRNA stability factor HuR (ELAV-L1) to drive cancer growth and progression. Here, we show that CRISPR-Cas9-mediated silencing of the HuR locus increases the relative sensitivity of PDAC cells to PARP inhibitors (PARPi). PDAC cells treated with PARPi stimulated translocation of HuR from the nucleus to the cytoplasm, specifically promoting stabilization of a new target, poly (ADP-ribose) glycohydrolase (PARG) mRNA, by binding a unique sequence embedded in its 3' untranslated region...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28684364/polyarginine-nanocapsules-a-versatile-nanocarrier-with-potential-in-transmucosal-drug-delivery
#15
Ana Gonzalez-Paredes, Dolores Torres, María José Alonso
The objective of this work was to investigate the potential utility of nanocapsules composed of an oily core decorated with a single polyarginine (PARG), or double PARG/polyacrylic acid (PAA) layer as oral peptide delivery carrier. A step-by-step formulation optimization process was designed, which involved the study of the influence of the surfactants, oils and polymer shells (PARG of different molecular weight and PAA) on the nanocapsules physicochemical properties, peptide loading efficiency, stability in simulated intestinal fluids (SIF) and capacity to enhance the permeability of the intestinal epithelium...
July 3, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28668129/what-combined-measurements-from-structures-and-imaging-tell-us-about-dna-damage-responses
#16
Chris A Brosey, Zamal Ahmed, Susan P Lees-Miller, John A Tainer
DNA damage outcomes depend upon the efficiency and fidelity of DNA damage responses (DDRs) for different cells and damage. As such, DDRs represent tightly regulated prototypical systems for linking nanoscale biomolecular structure and assembly to the biology of genomic regulation and cell signaling. However, the dynamic and multifunctional nature of DDR assemblies can render elusive the correlation between the structures of DDR factors and specific biological disruptions to the DDR when these structures are altered...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28525621/from-the-cover-ros-induced-store-operated-ca2-entry-coupled-to-parp-1-hyperactivation-is-independent-of-parg-activity-in-necrotic-cell-death
#17
Frances M Munoz, Fengjiao Zhang, Argel Islas-Robles, Serrine S Lau, Terrence J Monks
2,3,5-tris(Glutathion-S-yl)hydroquinone, a potent nephrotoxic and nephrocarcinogenic metabolite of benzene and hydroquinone, generates reactive oxygen species (ROS) causing DNA strand breaks and the subsequent activation of DNA repair enzymes, including poly(ADP-ribose) polymerase (PARP)-1. Under robust oxidative DNA damage, PARP-1 is hyperactivated, resulting in the depletion of NAD+ and ATP with accompanying elevations in intracellular calcium concentrations (iCa2+), and ultimately necrotic cell death. The role of Ca2+ during PARP-dependent necrotic cell death remains unclear...
August 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28503382/poly-adp-ribosylation-is-present-in-murine-sciatic-nerve-fibers-and-is-altered-in-a-charcot-marie-tooth-1e-neurodegenerative-model
#18
Laura I Lafon Hughes, Carlos J Romeo Cardeillac, Karina B Cal Castillo, Salomé C Vilchez Larrea, José R Sotelo Sosa, Gustavo A Folle Ungo, Silvia H Fernández Villamil, Alejandra E Kun González
BACKGROUND: Poly-ADP-ribose (PAR) is a polymer synthesized by poly-ADP-ribose polymerases (PARPs) as a postranslational protein modification and catabolized mainly by poly-ADP-ribose glycohydrolase (PARG). In spite of the existence of cytoplasmic PARPs and PARG, research has been focused on nuclear PARPs and PAR, demonstrating roles in the maintenance of chromatin architecture and the participation in DNA damage responses and transcriptional regulation. We have recently detected non-nuclear PAR structurally and functionally associated to the E-cadherin rich zonula adherens and the actin cytoskeleton of VERO epithelial cells...
2017: PeerJ
https://www.readbyqxmd.com/read/28415460/poly-arginine-graphene-quantum-dots-as-a-biocompatible-and-non-toxic-nanocomposite-layer-by-layer-electrochemical-preparation-characterization-and-non-invasive-malondialdehyde-sensory-application-in-exhaled-breath-condensate
#19
Mohammad Hasanzadeh, Fozieh Mokhtari, Nasrin Shadjou, Aziz Eftekhari, Ahad Mokhtarzadeh, Vahid Jouyban-Gharamaleki, Soltanali Mahboob
This study reports on the electropolymerization of a low toxic and biocompatible polymer with entitle poly arginine-graphene quantum dots (PARG-GQDs) as a novel strategy for surface modification of glassy carbon (GC) surface and preparation a new interface for biomedical application. The fabrication of PARG-GQDs on GCE was performed using Layer-by-layer regime. Scanning electron microscopy (SEM) was confirmed dispersion of GQDs on the surface of PARG which lead to increase of surface coverage of PARG. The redox behavior of prepared sensor was then characterized by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and chronoamperometry (CHA), square wave voltammetry (SWV), linear sweep voltammetry (LSV)...
June 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28254358/specific-killing-of-dna-damage-response-deficient-cells-with-inhibitors-of-poly-adp-ribose-glycohydrolase
#20
Polly Gravells, Emma Grant, Kate M Smith, Dominic I James, Helen E Bryant
Poly(ADP-ribosylation) of proteins following DNA damage is well studied and the use of poly(ADP-ribose) polymerase (PARP) inhibitors as therapeutic agents is an exciting prospect for the treatment of many cancers. Poly(ADP-ribose) glycohydrolase (PARG) has endo- and exoglycosidase activities which can cleave glycosidic bonds, rapidly reversing the action of PARP enzymes. Like addition of poly(ADP-ribose) (PAR) by PARP, removal of PAR by PARG is also thought to be required for repair of DNA strand breaks and for continued replication at perturbed forks...
April 2017: DNA Repair
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