- Bacterial-derived uracil as a modulator of mucosal immunity and gut-microbe homeostasis in Drosophila
Kyung Ah Lee
School of Biological Science, Seoul National University and National Creative Research Initiative Center for Symbiosystem, Seoul 151 742, South Korea
Cell 153:797-811. 2013
..Here, we show that bacterial-derived uracil acts as a ligand for dual oxidase (DUOX)-dependent reactive oxygen species generation in Drosophila gut and that ..
- Characterization of the gene cluster responsible for cylindrospermopsin biosynthesis
Troco Kaan Mihali
The University of New South Wales, School of Biotechnology and Biomolecular Sciences, Sydney, New South Wales 2052, Australia
Appl Environ Microbiol 74:716-22. 2008
..The uracil ring is formed by a novel pyrimidine biosynthesis mechanism and tailoring reactions, including sulfation and ..
- Dynamic contrast-enhanced magnetic resonance imaging biomarkers predict survival and response in hepatocellular carcinoma patients treated with sorafenib and metronomic tegafur/uracil
Chao Yu Hsu
Department of Radiology, College of Medicine, National Taiwan University, Taipei, Taiwan
J Hepatol 55:858-65. 2011
Sorafenib plus metronomic tegafur/uracil therapy can induce tumor stabilization in advanced hepatocellular carcinoma (HCC) patients...
- Repair and genetic consequences of endogenous DNA base damage in mammalian cells
Deborah E Barnes
Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
Annu Rev Genet 38:445-76. 2004
..The genetic instability characteristic of cancer cells may be due, in part, to mutations in genes whose products normally function to ensure DNA integrity...
- Cylindrospermopsin: occurrence, methods of detection and toxicology
CIMAR CIIMAR Laboratory of Ecotoxicology, Genomics and Evolution, Porto University, Porto, Portugal
J Appl Microbiol 114:605-20. 2013
..It is important to review the information regarding the findings made until now about this cyanotoxin 30 years since its first report...
- The cylindrospermopsin gene cluster of Aphanizomenon sp. strain 10E6: organization and recombination
Department of Biology, Microbial Evolution Research Group, University of Oslo, 0316 Oslo, Norway
Microbiology 156:2438-51. 2010
- Advancing uracil-excision based cloning towards an ideal technique for cloning PCR fragments
Hussam H Nour-Eldin
Plant Biochemistry Laboratory, Center for Molecular Plant Physiology, The Royal Veterinary and Agricultural University, Thorvaldsensvej 40, DK 1871 Frederiksberg C, Denmark
Nucleic Acids Res 34:e122. 2006
The largely unused uracil-excision molecular cloning technique has excellent features in most aspects compared to other modern cloning techniques...
- Genotoxicity of a freshwater cyanotoxin, cylindrospermopsin, in two human cell lines: Caco-2 and HepaRG
Agence Francaise de Securite Sanitaire des Aliments, Unité de Toxicologie Génétique des Contaminants Alimentaires, Fougeres, France
Environ Mol Mutagen 51:251-9. 2010
..Moreover, ketoconazole reduced both the genotoxicity and cytotoxicity caused by CYN. Our results confirm the involvement of metabolic activation of CYN in mediating its toxicity and suggest that CYN is progenotoxic...
- Patient preference and pharmacokinetics of oral modulated UFT versus intravenous fluorouracil and leucovorin: a randomised crossover trial in advanced colorectal cancer
M M Borner
Early Clinical Studies Group of The European Organization for Research and Treatment of Cancer, Belgium
Eur J Cancer 38:349-58. 2002
..v. 5-FU/LV. Oral UFT/LV compares favourably with i.v. 5-FU/LV in terms of toxicity and patient's preference and leads to prolonged 5-FU exposure, which is comparable to continuous i.v. 5-FU treatment...
- The versatile thymine DNA-glycosylase: a comparative characterization of the human, Drosophila and fission yeast orthologs
Institute of Molecular Cancer Research, University of Zurich, August Forel Strasse 7, Ch 8008 Zurich, Switzerland
Nucleic Acids Res 31:2261-71. 2003
Human thymine-DNA glycosylase (TDG) is well known to excise thymine and uracil from G.T and G...
- Uracil in DNA--occurrence, consequences and repair
Hans E Krokan
Institute of Cancer Research and Molecular Biology, Norwegian University of Science and Technology, N 7489 Trondheim, Norway
Oncogene 21:8935-48. 2002
b>Uracil in DNA results from deamination of cytosine, resulting in mutagenic U : G mispairs, and misincorporation of dUMP, which gives a less harmful U : A pair...
- Identification and characterization of a novel human DNA glycosylase for repair of cytosine-derived lesions
Tapas K Hazra
Department of Human Biological Chemistry and Genetics, Sealy Center for Molecular Science, University of Texas Medical Branch, 6 136 Medical Research Building, Rte 1079, Galveston, TX 77555, USA
J Biol Chem 277:30417-20. 2002
..Despite the absence of a putative nuclear localization signal, NEIL2 was predominantly localized in the nucleus. These results suggest that NEIL2 is involved in global genome repair mainly for removing oxidative products of cytosine...
- Uracil in DNA and its processing by different DNA glycosylases
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7489 Trondheim, Norway
Philos Trans R Soc Lond B Biol Sci 364:563-8. 2009
b>Uracil in DNA may result from incorporation of dUMP during replication and from spontaneous or enzymatic deamination of cytosine, resulting in U:A pairs or U:G mismatches, respectively...
- Concentrations of particulate and dissolved cylindrospermopsin in 21 Aphanizomenon-dominated temperate lakes
Brandenburg University of Technology, Department of Freshwater Conservation, Bad Saarow Research Station, Seestrasse 45, 15526 Bad Saarow, Germany
Toxicon 50:800-9. 2007
..It occurred in 98 CYN-positive samples, was the most abundant Nostocales and was the only Nostocales in five samples. This indicates that A. gracile is a potential CYN producer in German lakes...
- A randomized trial of adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung
Department of Surgery, Tokyo Medical University, Tokyo, Japan
N Engl J Med 350:1713-21. 2004
..In a previous phase 3 trial of adjuvant chemotherapy after resection of non-small-cell lung cancer, a combination of uracil and tegafur (often referred to as UFT) taken orally was shown to prolong survival...
- Cylindrospermopsin induced DNA damage and alteration in the expression of genes involved in the response to DNA damage, apoptosis and oxidative stress
National Institute of Biology, Department for Genetic Toxicology and Cancer Biology, Vecna pot 111, 1000 Ljubljana, Slovenia
Toxicon 58:471-9. 2011
..These results provide strong evidence that CYN should be considered as genotoxic and that lymphocytes can also be a target of cylindrospermopsin induced genotoxicity...
- A novel prokaryotic L-arginine:glycine amidinotransferase is involved in cylindrospermopsin biosynthesis
School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
FEBS J 277:3844-60. 2010
- urg1: a uracil-regulatable promoter system for fission yeast with short induction and repression times
Cancer Research United Kingdom Fission Yeast Functional Genomics Group, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom
PLoS ONE 3:e1428. 2008
..Given the short cell cycle of fission yeast, however, a promoter system that can be rapidly regulated, similar to the GAL system for budding yeast, would provide a key advantage for many experiments...
- Enzymatic capture of an extrahelical thymine in the search for uracil in DNA
Jared B Parker
Department of Pharmacology and Molecular Sciences, Johns Hopkins Medical School, 725 North Wolfe Street, Baltimore, Maryland 21205, USA
Nature 449:433-7. 2007
The enzyme uracil DNA glycosylase (UNG) excises unwanted uracil bases in the genome using an extrahelical base recognition mechanism...
- DNA-uracil and human pathology
Mirta M L Sousa
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, N 7006 Trondheim, Norway
Mol Aspects Med 28:276-306. 2007
b>Uracil is usually an inappropriate base in DNA, but it is also a normal intermediate during somatic hypermutation (SHM) and class switch recombination (CSR) in adaptive immunity...
- Alogliptin added to insulin therapy in patients with type 2 diabetes reduces HbA(1C) without causing weight gain or increased hypoglycaemia
Dallas Diabetes and Endocrine Center, Dallas, TX 75230, USA
Diabetes Obes Metab 11:1145-52. 2009
..To assess the efficacy and safety of alogliptin added to insulin in patients with type 2 diabetes inadequately controlled with insulin alone or combined with metformin...
- Uracil residues dependent on the deaminase AID in immunoglobulin gene variable and switch regions
Robert W Maul
Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA
Nat Immunol 12:70-6. 2011
Activation-induced deaminase (AID) initiates diversity of immunoglobulin genes through deamination of cytosine to uracil. Two opposing models have been proposed for the deamination of DNA or RNA by AID...
- Uracil DNA glycosylase uses DNA hopping and short-range sliding to trap extrahelical uracils
Rishi H Porecha
Department of Pharmacology and Molecular Sciences, The Johns Hopkins School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA
Proc Natl Acad Sci U S A 105:10791-6. 2008
..One example is the enzyme uracil DNA glycosylase (UNG), which captures and excises rare extrahelical uracil bases that have emerged from the DNA ..
- Origin of endogenous DNA abasic sites in Saccharomyces cerevisiae
CEA, DSV, Departement de Radiobiologie et Radiopathologie, UMR 217 CNRS CEA Radiobiologie Moléculaire et Cellulaire, F 92265 Fontenay aux Roses, France
Mol Cell Biol 23:8386-94. 2003
..Our results show that the deletion of the UNG1 gene encoding the uracil DNA glycosylase suppresses the lethality of the apn1 apn2 rad1 mutant...
- Phase II study of combining sorafenib with metronomic tegafur/uracil for advanced hepatocellular carcinoma
Chih Hung Hsu
Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
J Hepatol 53:126-31. 2010
..Metronomic chemotherapy using tegafur/uracil (4:1 molar ratio), an oral fluoropyrimidine, has been shown to enhance the anti-tumor effect of anti-angiogenic ..
- Oxidative stress responses in tilapia (Oreochromis niloticus) exposed to a single dose of pure cylindrospermopsin under laboratory conditions: influence of exposure route and time of sacrifice
Area of Toxicology, Faculty of Pharmacy, Profesor García González 2, 41012 Seville, Spain
Aquat Toxicol 105:100-6. 2011
..The time of sacrifice had a bigger influence on the results than the exposure route because after 5 days some of the biomarkers assayed had recovered their pre-intoxication levels, which was not the case after 24 h...
- Identification of the first pyrimidine nucleobase transporter in Leishmania: similarities with the Trypanosoma brucei U1 transporter and antileishmanial activity of uracil analogues
I G Papageorgiou
Department of Biochemistry, Hellenic Pasteur Institute, 115 21 Athens, Greece
Parasitology 130:275-83. 2005
..Here, we report a Leishmania major transporter with high affinity for uracil (Km=0.32+/-0.07 microM) which we designated LmU1...
- A second pathway to degrade pyrimidine nucleic acid precursors in eukaryotes
Department of Cell and Organism Biology, Lund University, 223 62 Lund, Sweden
J Mol Biol 380:656-66. 2008
..In eukaryotes, degradation of uracil has been believed to proceed only via the reduction to dihydrouracil...
- Genotoxic effects of the cyanobacterial hepatotoxin cylindrospermopsin in the HepG2 cell line
Department for Genetic Toxicology and Cancer Biology, National Institute of Biology, Vecna pot 111, 1000 Ljubljana, Slovenia
Arch Toxicol 85:1617-26. 2011
..Our results provide new evidence that CYN is genotoxic and strongly suggest that it needs to be considered in the human health risk assessment...
- Efficacy and safety of alogliptin added to pioglitazone in Japanese patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial with an open-label long-term extension study
Diabetes and Endocrine Division, Kawasaki Medical School, Okayama, Japan
Diabetes Obes Metab 13:1028-35. 2011
..To assess the efficacy and safety of alogliptin added to pioglitazone versus pioglitazone monotherapy, in Japanese patients with type 2 diabetes who achieved inadequate glycaemic control on pioglitazone plus diet/exercise...
- Structure and mechanism of the uracil transporter UraA
State Key Laboratory of Bio membrane and Membrane Biotechnology, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China
Nature 472:243-6. 2011
..Here we report the crystal structure of a representative NAT protein, the Escherichia coli uracil/H(+) symporter UraA, in complex with uracil at a resolution of 2.8 Å...
- Oral uracil and tegafur plus leucovorin compared with intravenous fluorouracil and leucovorin in stage II and III carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project Protocol C-06
Barry C Lembersky
National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA 15212, USA
J Clin Oncol 24:2059-64. 2006
The primary aim of this study was to compare the relative efficacy of oral uracil and tegafur (UFT) plus leucovorin (LV) with the efficacy of weekly intravenous fluorouracil (FU) plus LV in prolonging disease-free survival (DFS) and ..
- Structure of the 16S rRNA pseudouridine synthase RsuA bound to uracil and UMP
Biotechnology Research Institute, 6100 Royalmount Avenue, Montreal, Quebec H4P 2R2, Canada
Nat Struct Biol 9:353-8. 2002
..We have determined the crystal structure of RsuA bound to uracil at 2.0 A resolution and to uridine 5'-monophosphate (UMP) at 2.65 A resolution...
- The influence of cylindrospermopsin on oxidative DNA damage and apoptosis induction in HepG2 cells
National Institute of Biology, Department of Genetic Toxicology and Cancer Biology, Vecna pot 111, 1000 Ljubljana, Slovenia
Chemosphere 92:24-30. 2013
- Efficacy and safety of alogliptin added to metformin in Japanese patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial with an open-label, long-term extension study
Kansai Electric Power Hospital, Osaka, Japan
Diabetes Obes Metab 14:927-36. 2012
..To evaluate the efficacy and safety of alogliptin added to metformin versus metformin monotherapy in Japanese patients with type 2 diabetes who achieved inadequate glycaemic control on metformin (500 or 750 mg/day) + diet/exercise...
- Uracil-containing DNA in Drosophila: stability, stage-specific accumulation, and developmental involvement
Institute of Enzymology, Research Center for Natural Sciences, Hungarian Academy of Science, Budapest, Hungary
PLoS Genet 8:e1002738. 2012
Base-excision repair and control of nucleotide pools safe-guard against permanent uracil accumulation in DNA relying on two key enzymes: uracil-DNA glycosylase and dUTPase...
- Nuclear localization of de novo thymidylate biosynthesis pathway is required to prevent uracil accumulation in DNA
Amanda J MacFarlane
Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA
J Biol Chem 286:44015-22. 2011
b>Uracil accumulates in DNA as a result of impaired folate-dependent de novo thymidylate biosynthesis, a pathway composed of the enzymes serine hydroxymethyltransferase (SHMT), thymidylate synthase (TYMS), and dihydrofolate reductase...
- Lowering of postprandial lipids in individuals with type 2 diabetes treated with alogliptin and/or pioglitazone: a randomised double-blind placebo-controlled study
Department of Molecular and Clinical Medicine, University of Gothenburg, Goteborg, Sweden
Diabetologia 55:915-25. 2012
..We assessed the effects of alogliptin (Alo) and Alo co-administered with pioglitazone (Pio) vs placebo (Pbo) on triacylglycerol (TG)-rich lipoproteins in type 2 diabetes before and following a high-fat meal...
- Specific binding of human MSH2.MSH6 mismatch-repair protein heterodimers to DNA incorporating thymine- or uracil-containing UV light photoproducts opposite mismatched bases
Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon 97331 7301, USA
J Biol Chem 274:16894-900. 1999
..Surprisingly, although hMutSalpha affinities for both non-photoproduct UU/GG double mismatches and for (uracil-cyclobutane-dimer)/AG single mismatches were high, affinity for the (uracil-cyclobutane-dimer)/GG mismatch was ..
- First observation of cylindrospermopsin in Anabaena lapponica isolated from the boreal environment (Finland)
Department of Biochemistry and Pharmacy, Abo Akademi University, Tykistokatu 6A, FI 20520 Turku, Finland
Environ Toxicol 21:552-60. 2006
..Cylindrospermopsin was confirmed by all three techniques in a culture sample of Anabaena lapponica at a concentration of 242 microg cylindrospermopsin per g freeze-dried cyanobacterial material...
- Cylindrospermopsin-induced protein synthesis inhibition and its dissociation from acute toxicity in mouse hepatocytes
Suzanne M Froscio
Department of Clinical and Experimental Pharmacology, University of Adelaide, Adelaide, South Australia 5005, Australia
Environ Toxicol 18:243-51. 2003
..In cell types deficient in CYP450 enzymes, protein synthesis inhibition may play a more crucial role in the development of cytotoxicity...
- Oral administration of uracil-tegafur (UFT) inhibits liver micrometastasis of human colon cancer in an orthotopic nude mouse model and its early detection system
Department of Surgical Oncology, Cancer Research Institute, Kanazawa University, 13 1 Takaramachi, Kanazawa 920 8640, Japan
Surg Today 34:855-9. 2004
To evaluate the effect of UFT (an oral antineoplastic drug combining uracil and tegafur) as an adjuvant chemotherapy.
- C(5) modified uracil derivatives showing antiproliferative and erythroid differentiation inducing activities on human chronic myelogenous leukemia K562 cells
BioPharmaNet, Department of Biochemistry and Molecular Biology, Molecular Biology Division, University of Ferrara, Via Luigi Borsari, 46 44100 Ferrara, Italy
Eur J Pharmacol 672:30-7. 2011
..In this paper we report a screening study on a set of different modified C(5) uracil derivatives for the evaluation of their antiproliferative effect in connection with erythroid differentiation ..
- A randomized consent design trial of neoadjuvant chemotherapy with tegafur plus uracil (UFT) for gastric cancer--a single institute study
Department of Cardiovascular and Digestive Surgery, Shimane University School of Medicine, Shimane, Japan
Anticancer Res 24:1879-87. 2004
..The present study was designed to assess the survival benefits of NAC with UFT (tegafur plus uracil) for gastric cancer, as a randomized consent trial as described by Zelen.
- dUTPase activity is critical to maintain genetic stability in Saccharomyces cerevisiae
CEA, DSV Département de Radiobiologie et Radiopathologie, UMR 217 CNRS Radiobiologie Moléculaire et Cellulaire, BP 6, 92265 Fontenay aux Roses, France
Nucleic Acids Res 34:2056-66. 2006
..All phenotypes of the dut1-1 mutant are suppressed by the simultaneous inactivation of the uracil DNA N-glycosylase, Ung1. However, the ung1 dut1-1 double mutant accumulates uracil in its genomic DNA...
- Uracil salvage is necessary for early Arabidopsis development
Samuel E Mainguet
URGV, UMR 1165 Institut National de la Recherche Agronomique CNRS, Evry Cedex, France
Plant J 60:280-91. 2009
..b>Uracil phosphoribosyltransferases (UPRTs; EC 2.4.2...
- UPS1 and UPS2 from Arabidopsis mediate high affinity transport of uracil and 5-fluorouracil
Plant Physiology, ZMBP, Auf der Morgenstelle 1, D 72076 Tubingen, Germany
J Biol Chem 279:44817-24. 2004
..uptake systems for pyrimidines have been described, but in higher eukaryotes, transporters for thymine and uracil have not been identified...
- Uracil in DNA: consequences for carcinogenesis and chemotherapy
Sondra H Berger
Department of Pharmaceutical and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, 715 Sumter Street, Columbia, SC 29208, USA
Biochem Pharmacol 76:697-706. 2008
..of the close relationship between dUMP and TMP, thymidylate stress is associated with increased incorporation of uracil into DNA. Genomic uracil is removed by uracil DNA glycosylases of base excision repair (BER)...
- Structure and function in the uracil-DNA glycosylase superfamily
L H Pearl
Section of Structural Biology and CRC DNA Repair Enzyme Group, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, SW3 6JB, London, UK
Mutat Res 460:165-81. 2000
Deamination of cytosine to uracil is one of the major pro-mutagenic events in DNA, causing G:C-->A:T transition mutations if not repaired before replication...
- Cylindrospermopsin genotoxicity and cytotoxicity: role of cytochrome P-450 and oxidative stress
Andrew R Humpage
Department of Clinical and Experimental Pharmacology, University of Adelaide, Adelaide, Australia
J Toxicol Environ Health A 68:739-53. 2005
..It therefore seems likely that CYP450-derived metabolites are responsible for both the acute cytotoxicity and genotoxicity induced by CYN...
- The Palm Island mystery disease 20 years on: a review of research on the cyanotoxin cylindrospermopsin
Dilwyn J Griffiths
School of Biological Sciences, James Cook University, Townsville 4811, Australia
Environ Toxicol 18:78-93. 2003
..Among the more recent developments described are those that come from the application of molecular techniques for characterizing toxic and nontoxic strains and for exploring the genetic aspects of CYN production...
- JBP1 and JBP2 are two distinct thymidine hydroxylases involved in J biosynthesis in genomic DNA of African trypanosomes
Laura J Cliffe
Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia 30602, USA
Nucleic Acids Res 37:1452-62. 2009
..Reintroduction of JBP2 in the J-null trypanosome stimulates HOMedU formation and site-specific synthesis of base J. We conclude that JBP2 and JBP1 are the TH enzymes involved in J biosynthesis...
- Pyrimidine salvage in Trypanosoma brucei bloodstream forms and the trypanocidal action of halogenated pyrimidines
Juma A M Ali
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, United Kingdom
Mol Pharmacol 83:439-53. 2013
..transport activities in bloodstream form Trypanosoma brucei brucei found that these cells express a high-affinity uracil transporter (designated TbU3) that is clearly distinct from the procyclic pyrimidine transporters...
- Molecular mechanisms of antibody somatic hypermutation
Javier M Di Noia
Institut de Recherches Cliniques de Montreal, H2W 1R7 Montréal, Quebec, Canada
Annu Rev Biochem 76:1-22. 2007
..Thus, DNA replication across the uracil yields transition mutations at C:G pairs, whereas uracil excision by UNG uracil-DNA glycosylase creates abasic ..
- An AbrB-like protein might be involved in the regulation of cylindrospermopsin production by Aphanizomenon ovalisporum
Department of Plant and Environmental Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
Environ Microbiol 10:988-99. 2008
..coli, include N-acetylation and methylation of specific residues. We discuss the possible role of these modifications in the regulation of cylindrospermopsin production in Aphanizomenon...
- Clinical studies of three oral prodrugs of 5-fluorouracil (capecitabine, UFT, S-1): a review
Groupe de RMN Biomédicale, Laboratoire des IMRCP, Universite Paul Sabatier, Toulouse, France
Oncologist 7:288-323. 2002
..e., capecitabine, UFT (ftorafur [FTO] plus uracil), and S-1 (FTO plus 5-chloro-2,4-dihydroxypyridine plus potassium oxonate)...
- A new class of uracil-DNA glycosylases related to human thymine-DNA glycosylase
Istituto di Richerche di Biologia Molecolare P Angeletti, Pomezia, Italy
Nature 383:735-8. 1996
Mispairs in DNA of guanine with uracil and thymine can arise as a result of deamination of cytosine and 5-methylcytosine, respectively. In humans such mispairs are removed by thymine-DNA glycosylase (TDG)...
- Gene-targeted mice lacking the Ung uracil-DNA glycosylase develop B-cell lymphomas
Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
Oncogene 22:5381-6. 2003
Mice deficient in the Ung uracil-DNA glycosylase have an increased level of uracil in their genome, consistent with a major role of Ung counteracting U:A base pairs arising by misincorporation of dUMP during DNA replication...
- The UA_handle: a versatile submotif in stable RNA architectures
Chemistry and Biochemistry Department, University of California, Santa Barbara, CA 93106 9510, USA
Nucleic Acids Res 37:215-30. 2009
..The sequence network resulting from the structural relationships shared by these RNA motifs can be used as a proto-language for assisting prediction and rational design of RNA tertiary structures...
- Uracil incorporation into genomic DNA does not predict toxicity caused by chemotherapeutic inhibition of thymidylate synthase
Department of Pharmaceutical and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA
DNA Repair (Amst) 7:162-9. 2008
..During TS inhibition, TTP levels decrease with a subsequent increase in dUTP. Uracil incorporated into the genome is removed by base excision repair (BER)...
- Base J: discovery, biosynthesis, and possible functions
Center of Biomedical Genetics, Division of Molecular Biology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
Annu Rev Microbiol 62:235-51. 2008
- Uracil in DNA--general mutagen, but normal intermediate in acquired immunity
Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, N 7006 Trondheim, Norway
DNA Repair (Amst) 6:505-16. 2007
..In both cases, uracil is mainly removed by a uracil-DNA glycosylase (UDG) that initiates the base excision repair pathway...
- Hierarchy of lesion processing governs the repair, double-strand break formation and mutability of three-lesion clustered DNA damage
Laura J Eccles
CRUK MRC Gray Institute for Radiation Oncology and Biology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK
Nucleic Acids Res 38:1123-34. 2010
..The inaccurate repair of such clusters has biological significance due to the ultimate risk of tumourigenesis or as potential cytotoxic lesions in tumour cells...
- Cylindrospermopsin: a decade of progress on bioaccumulation research
Centre for Environmental Management, CQUniversity Australia, Building 7, Bruce Highway, North Rockhampton, Queensland 4702, Australia
Mar Drugs 8:542-64. 2010
..A discussion on the factors influencing bioaccumulation rates and potential is also provided, along with notes on detection, monitoring and risk assessments. Finally, key gaps in the existing research are identified for future study...
- A mutant Pfu DNA polymerase designed for advanced uracil-excision DNA engineering
Morten H H Nørholm
Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, SE 10691 Stockholm, Sweden
BMC Biotechnol 10:21. 2010
..b>Uracil-excision based cloning is ligase and sequence independent and allows seamless fusion of multiple DNA sequences in ..
- Uracil-DNA glycosylase (UNG)-deficient mice reveal a primary role of the enzyme during DNA replication
Imperial Cancer Research Fund, Clare Hall Laboratories, Hertfordshire, United Kingdom
Mol Cell 5:1059-65. 2000
Gene-targeted knockout mice have been generated lacking the major uracil-DNA glycosylase, UNG. In contrast to ung- mutants of bacteria and yeast, such mice do not exhibit a greatly increased spontaneous mutation frequency...
- Keeping uracil out of DNA: physiological role, structure and catalytic mechanism of dUTPases
Beata G Vertessy
Institute of Enzymology, Hungarian Academy of Sciences, Budapest, Hungary
Acc Chem Res 42:97-106. 2009
The thymine-uracil exchange constitutes one of the major chemical differences between DNA and RNA...
- Attenuated virulence of uridine-uracil auxotrophs of Aspergillus fumigatus
Laboratoire des Aspergillus and Unité d Histopathologie, Institut Pasteur, Paris, France
Infect Immun 64:4401-5. 1996
..mutation in the pyrG gene encoding orotidine-5'-phosphate decarboxylase (and therefore auxotrophic for uridine or uracil) were evaluated in a murine model of invasive aspergillosis...
- Human activation-induced cytidine deaminase causes transcription-dependent, strand-biased C to U deaminations
Department of Chemistry, Wayne State University, Detroit, MI 48202, USA
Nucleic Acids Res 31:2990-4. 2003
..It suggests that AID may be recruited to variable genes through transcription without the assistance of other proteins and that the strand bias in SHM may be caused by the preference of AID for the non-transcribed strand...
- Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: The Japan Clinical Oncology Group Study (JCOG9205)
Division of Gastrointestinal Oncology Digestive Endoscopy, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
J Clin Oncol 21:54-9. 2003
To compare fluorouracil (FU) alone with FU plus cisplatin (FP) and with uracil and tegafur plus mitomycin (UFTM) for patients with advanced gastric cancer in a prospective, randomized, controlled trial.
- Incorporation of uracil into minus strand DNA affects the specificity of plus strand synthesis initiation during lentiviral reverse transcription
George J Klarmann
Eccles Institute of Human Genetics and the Department of Biochemistry, University of Utah, Salt Lake City 84112, USA
J Biol Chem 278:7902-9. 2003
Many retroviruses either encode dUTP pyrophosphatase (dUTPase) or package host-derived uracil DNA glycosylase as a means to limit the accumulation of uracil in DNA strands, suggesting that uracil is detrimental to one or more steps in the ..
- Uracil recognition in archaeal DNA polymerases captured by X-ray crystallography
Susan J Firbank
Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
J Mol Biol 381:529-39. 2008
Archaeal family B DNA polymerases bind tightly to template-strand uracil and stall replication on encountering the pro-mutagenic base. This article describes an X-ray crystal structure, at 2...
- Uracil metabolism--UMP synthesis from orotic acid or uridine and conversion of uracil to beta-alanine: enzymes and cDNAs
T W Traut
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599, USA
Prog Nucleic Acid Res Mol Biol 53:1-78. 1996
- Improved survival for hepatocellular carcinoma with portal vein tumor thrombosis treated by intra-arterial chemotherapy combining etoposide, carboplatin, epirubicin and pharmacokinetic modulating chemotherapy by 5-FU and enteric-coated tegafur/uracil: a p
Department of Gastroenterology and Hepatology, Saiseikai Niigata Second Hospital, Teraji 280 7, Niigata 950 1104, Japan
World J Gastroenterol 13:5465-70. 2007
..To investigate the poor prognosis of HCC with PVTT, we evaluated the efficacy by a new combination chemotherapy for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT)...
- Single-nucleotide and long-patch base excision repair of DNA damage in plants
Department of Genetics, University of Cordoba, 14071 Cordoba, Spain
Plant J 60:716-28. 2009
..cell extracts contain the enzymatic machinery required to completely repair ubiquitous DNA lesions, such as uracil and abasic (AP) sites...
- Phenotypical variation in a toxic strain of the phytoplankter, Cylindrospermopsis raciborskii (Nostocales, Cyanophyceae) during batch culture
P R Hawkins
Sydney Water Corporation, 51 Hermitage Road, West Ryde, NSW, 2114 Australia
Environ Toxicol 16:460-7. 2001
..The application of algicides that promote cell lysis will exacerbate this effect...
- Effect of alogliptin, pioglitazone and glargine on pancreatic β-cells in diabetic db/db mice
Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2 2 Yamadaoka, Suita City, Osaka 565 0871, Japan
Biochem Biophys Res Commun 404:534-40. 2011
..To examine if anti-diabetic reagents, such as insulin, pioglitazone (pio), and alogliptin (alo), have protective effects on β-cell mass and function in vivo, we treated obese diabetic db/db mice with these reagents...
- Increased uracil insertion in DNA is cytotoxic and increases the frequency of mutation, double strand break formation and VSG switching in Trypanosoma brucei
Victor M Castillo-Acosta
Instituto de Parasitologia y Biomedicina Lopez Neyra, Consejo Superior de Investigaciones Cientificas, Parque Tecnológico de Ciencias de la Salud, Avenida del Conocimiento, s n 18100 Armilla, Granada, Spain
DNA Repair (Amst) 11:986-95. 2012
Deoxyuridine 5'-triphosphate pyrophosphatase (dUTPase) and uracil-DNA glycosylase (UNG) are key enzymes involved in the control of the presence of uracil in DNA...
- Efficacy and tolerability of the DPP-4 inhibitor alogliptin combined with pioglitazone, in metformin-treated patients with type 2 diabetes
R A DeFronzo
University of Texas Health Sciences Center, Diabetes Division, 7703 Floyd Curl Drive, San Antonio, Texas 78229, USA
J Clin Endocrinol Metab 97:1615-22. 2012
..Optimal management of type 2 diabetes remains an elusive goal. Combination therapy addressing the core defects of impaired insulin secretion and insulin resistance shows promise in maintaining glycemic control...
- Removal of uracil by uracil DNA glycosylase limits pemetrexed cytotoxicity: overriding the limit with methoxyamine to inhibit base excision repair
A D Bulgar
Department of Medicine, Division of Hematology Oncology, Case Western Reserve University, Cleveland, OH, USA
Cell Death Dis 3:e252. 2012
b>Uracil DNA glycosylase (UDG) specifically removes uracil bases from DNA, and its repair activity determines the sensitivity of the cell to anticancer agents that are capable of introducing uracil into DNA...
- Biosynthesis of cylindrospermopsin and 7-epicylindrospermopsin in Oscillatoria sp. strain PCC 6506: identification of the cyr gene cluster and toxin analysis
Laboratoire Charles Friedel, UMR CNRS 7223, ENSCP ChimieParisTech, 11 rue Pierre et Marie Curie, 75231 Paris Cedex 05, France
Appl Environ Microbiol 76:4943-9. 2010
..All the cylindrospermopsin producers studied gave a PCR product using specific primers for the amplification of the cyrJ gene from genomic DNA...
- Unwinding of primer-templates by archaeal family-B DNA polymerases in response to template-strand uracil
Tomas T Richardson
Institute of Cell and Molecular Biosciences ICaMB, The University of Newcastle, Newcastle upon Tyne NE2 4HH, UK
Nucleic Acids Res 41:2466-78. 2013
Archaeal family-B DNA polymerases bind tightly to deaminated bases and stall replication on encountering uracil in template strands, four bases ahead of the primer-template junction...
- Vaccinia virus uracil DNA glycosylase interacts with the A20 protein to form a heterodimeric processivity factor for the viral DNA polymerase
Eleni S Stanitsa
Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
J Biol Chem 281:3439-51. 2006
..A20 has been shown to interact with D4, the virally encoded uracil DNA glycosylase (UDG), by yeast-two hybrid and in vitro analysis...
- Distribution of 14C cylindrospermopsin in vivo in the mouse
R L Norris
National Research Centre for Environmental Toxicology, 39 Kessels Road, Coopers Plains, QLD 4108 Australia
Environ Toxicol 16:498-505. 2001
..There is at least one methanol-extractable metabolite as well as a nonmethanol-extractable metabolite in the liver. The methanol-extractable metabolite was not found in the kidney and is more hydrophilic than CYN itself on reverse phase...
- Discovery of alogliptin: a potent, selective, bioavailable, and efficacious inhibitor of dipeptidyl peptidase IV
J Med Chem 50:2297-300. 2007
..Alogliptin is currently undergoing phase III trials in patients with type 2 diabetes...
- AR-C155858 is a potent inhibitor of monocarboxylate transporters MCT1 and MCT2 that binds to an intracellular site involving transmembrane helices 7-10
Matthew J Ovens
Department of Biochemistry, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK
Biochem J 425:523-30. 2010
..Biol. Chem. 284, 20011-20021]...
- Phylogenomic analysis of the uracil-DNA glycosylase superfamily
J Ignacio Lucas-Lledó
Department of Biology, Indiana University Bloomington, Indiana, USA
Mol Biol Evol 28:1307-17. 2011
The spontaneous deamination of cytosine produces uracil mispaired with guanine in DNA, which will produce a mutation, unless repaired...
- First occurrence of cylindrospermopsin in freshwater in France
Université de Rennes U M R, CNRS Ecobio I F R CAREN, France
Environ Toxicol 24:415-20. 2009
..55 and 1.95 microg/L. The occurrence of CYN represents an additional health hazard to MC especially because Aphanizomenon flos-aquae is the third most common species in freshwaters in France...
- Stressing-out DNA? The contribution of serine-phosphodiester interactions in catalysis by uracil DNA glycosylase
R M Werner
Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute and National Institute for Standards and Technology, 9600 Gudelsky Drive, Rockville, Maryland 20850, USA
Biochemistry 39:12585-94. 2000
The DNA repair enzyme uracil DNA glycosylase (UDG) pinches the phosphodiester backbone of damaged DNA using the hydroxyl side chains of a conserved trio of serine residues, resulting in flipping of the deoxyuridine from the DNA helix into ..
- Distinction and relationship between elongation rate and processivity of RNA polymerase II in vivo
Paul B Mason
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
Mol Cell 17:831-40. 2005
..Our results suggest that, in vivo, a reduced rate of Pol II elongation leads to premature dissociation along the chromatin template and that Pol II processivity can be uncoupled from elongation rate...
- Time-dependent histopathological changes induced in Tilapia (Oreochromis niloticus) after acute exposure to pure cylindrospermopsin by oral and intraperitoneal route
Area of Toxicology, Faculty of Pharmacy, University of Seville, Profesor García González 2, 41012 Seville, Spain
Ecotoxicol Environ Saf 76:102-13. 2012
..p. route, and with the time of sacrifice, supporting the histopathological results obtained in these organs. Thus, both parameters could be useful for quantifying the extent of the damage in fish after CYN exposure...
- Mimicking damaged DNA with a small molecule inhibitor of human UNG2
Daniel J Krosky
Department of Pharmacology and Molecular Sciences, 725 North Wolfe Street, Baltimore, MD 21205, USA
Nucleic Acids Res 34:5872-9. 2006
Human nuclear uracil DNA glycosylase (UNG2) is a cellular DNA repair enzyme that is essential for a number of diverse biological phenomena ranging from antibody diversification to B-cell lymphomas and type-1 human immunodeficiency virus ..
- RutR is the uracil/thymine-sensing master regulator of a set of genes for synthesis and degradation of pyrimidines
Department of Frontier Bioscience and Micro Nano Technology Research Centre, Hosei University, Koganei, Tokyo 184 8584, Japan
Mol Microbiol 66:744-57. 2007
..Adding either uracil or thymine abolished RutR binding in vitro to the carAB P1 promoter...
- Presteady-state analysis of a single catalytic turnover by Escherichia coli uracil-DNA glycosylase reveals a "pinch-pull-push" mechanism
Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon 97331, USA
J Biol Chem 277:19424-32. 2002
b>Uracil-DNA glycosylase catalyzes the excision of uracils from DNA via a mechanism where the uracil is extrahelically flipped out of the DNA helix into the enzyme active site...
- Heteronuclear NMR and crystallographic studies of wild-type and H187Q Escherichia coli uracil DNA glycosylase: electrophilic catalysis of uracil expulsion by a neutral histidine 187
A C Drohat
Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, National Institute for Standards and Technology, Rockville, Maryland 20850, USA
Biochemistry 38:11876-86. 1999
The nature of the putative general acid His187 in the reaction catalyzed by Escherichia coli uracil DNA glycosylase (UDG) was investigated using X-ray crystallography and NMR spectroscopy...
- Reducing sequence artifacts in amplicon-based massively parallel sequencing of formalin-fixed paraffin-embedded DNA by enzymatic depletion of uracil-containing templates
Molecular Pathology Research and Development Laboratory, Department of Pathology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
Clin Chem 59:1376-83. 2013
..Pretreatment of FFPE DNA with uracil-DNA glycosylase (UDG) can markedly reduce these C:G>T:A SNCs with a small panel of amplicons...
- Strikingly different properties of uracil-DNA glycosylases UNG2 and SMUG1 may explain divergent roles in processing of genomic uracil
Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
DNA Repair (Amst) 11:587-93. 2012
Genomic uracil resulting from spontaneously deaminated cytosine generates mutagenic U:G mismatches that are usually corrected by error-free base excision repair (BER)...
- Comparative pharmacokinetic study of continuous venous infusion fluorouracil and oral fluorouracil with eniluracil in patients with advanced solid tumors
Alex A Adjei
Mayo Clinic and Foundation, Department of Oncology, Rochester, MN 55905, USA
J Clin Oncol 20:1683-91. 2002
..To compare the pharmacokinetics of continuous venous infusion (CVI) fluorouracil (5-FU) with that of oral eniluracil/5-FU and to describe toxicities and clinical activity of prolonged oral administration of eniluracil/5-FU...
- Associations between two common variants C677T and A1298C in the methylenetetrahydrofolate reductase gene and measures of folate metabolism and DNA stability (strand breaks, misincorporated uracil, and DNA methylation status) in human lymphocytes in vivo
Division of Cellular Integrity, Rowett Research Institute, Bucksburn, Aberdeen, United Kingdom
Cancer Epidemiol Biomarkers Prev 13:1436-43. 2004
..between two variants of the MTHFR gene (C677T and A1298C) and blood folate, homocysteine, and genomic stability (strand breakage, misincorporated uracil, and global cytosine methylation in lymphocytes) in a study of 199 subjects.
- Oral toxicity of the cyanobacterial toxin cylindrospermopsin in male Swiss albino mice: determination of no observed adverse effect level for deriving a drinking water guideline value
A R Humpage
Australian Water Quality Centre, Cooperative Research Centre for Water Quality and Treatment, Private Bag 3, Salisbury, South Australia 5108
Environ Toxicol 18:94-103. 2003
- Two thymidine hydroxylases differentially regulate the formation of glucosylated DNA at regions flanking polymerase II polycistronic transcription units throughout the genome of Trypanosoma brucei
Laura J Cliffe
Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, USA
Nucleic Acids Res 38:3923-35. 2010
..The regulation of J synthesis/localization by two THs and potential biological function of J in regulating kinetoplastid gene expression is discussed...