Genomes and Genes
Summary: Cytosine nucleotides which contain deoxyribose as the sugar moiety.
- Bose Basu B, Derose E, Kirby T, Mueller G, Beard W, Wilson S, et al. Dynamic characterization of a DNA repair enzyme: NMR studies of [methyl-13C]methionine-labeled DNA polymerase beta. Biochemistry. 2004;43:8911-22 pubmed..Thus, the NMR data indicate that the nucleotide-DNA interaction appears to be essential for conformational activation. ..
- Rechkoblit O, Malinina L, Cheng Y, Kuryavyi V, Broyde S, Geacintov N, et al. Stepwise translocation of Dpo4 polymerase during error-free bypass of an oxoG lesion. PLoS Biol. 2006;4:e11 pubmed
- Choi J, Angel K, Guengerich F. Translesion synthesis across bulky N2-alkyl guanine DNA adducts by human DNA polymerase kappa. J Biol Chem. 2006;281:21062-72 pubmed
- Datta N, Shewach D, Mitchell B, Fox I. Kinetic properties and inhibition of human T lymphoblast deoxycytidine kinase. J Biol Chem. 1989;264:9359-64 pubmed..While many different nucleotides potently inhibit deoxycytidine kinase, their low intracellular concentrations make their regulatory role less important. ..
- Kohalmi S, Glattke M, McIntosh E, Kunz B. Mutational specificity of DNA precursor pool imbalances in yeast arising from deoxycytidylate deaminase deficiency or treatment with thymidylate. J Mol Biol. 1991;220:933-46 pubmed..We consider several possibilities, including potential roles for the regulation and specificity of proofreading and for mismatch correction. ..
- Ferraro P, Franzolin E, Pontarin G, Reichard P, Bianchi V. Quantitation of cellular deoxynucleoside triphosphates. Nucleic Acids Res. 2010;38:e85 pubmed publisher..We suggest that in some earlier reports ribonucleotide incorporation may have caused too high values for dGTP and dCTP. ..
- Roettger M, Fiala K, Sompalli S, Dong Y, Suo Z. Pre-steady-state kinetic studies of the fidelity of human DNA polymerase mu. Biochemistry. 2004;43:13827-38 pubmed..In addition to a slow and distributive DNA polymerase activity, Polmu was identified to possess a weak strand-displacement activity. The potential biological roles of Polmu are discussed. ..
- Ferraro P, Nicolosi L, Bernardi P, Reichard P, Bianchi V. Mitochondrial deoxynucleotide pool sizes in mouse liver and evidence for a transport mechanism for thymidine monophosphate. Proc Natl Acad Sci U S A. 2006;103:18586-91 pubmed..At nM external dTMP the nucleotide is concentrated 100-fold inside the mt matrix. Export of thymidine phosphates was much slower and possibly occurred at the level of dTDP. ..
- Nair D, Johnson R, Prakash L, Prakash S, Aggarwal A. Human DNA polymerase iota incorporates dCTP opposite template G via a G.C + Hoogsteen base pair. Structure. 2005;13:1569-77 pubmed..A G.C+ Hoogsteen base pair suggests a specific mechanism for hPoliota's ability to bypass N(2)-adducted guanines that obstruct replication. ..
- Gonzalez Vioque E, Torres Torronteras J, Andreu A, Marti R. Limited dCTP availability accounts for mitochondrial DNA depletion in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). PLoS Genet. 2011;7:e1002035 pubmed publisher..Thus, therapy approaches focusing on restoring the deficient substrates should be explored. ..
- Yang G, Franklin M, Li J, Lin T, Konigsberg W. A conserved Tyr residue is required for sugar selectivity in a Pol alpha DNA polymerase. Biochemistry. 2002;41:10256-61 pubmed
- Nelson J, Lawrence C, Hinkle D. Deoxycytidyl transferase activity of yeast REV1 protein. Nature. 1996;382:729-31 pubmed..Insertion of cytosine opposite an abasic site produced a terminus that was extended efficiently by Pol-zeta, but not by yeast Pol-alpha. ..
- Einolf H, Guengerich F. Kinetic analysis of nucleotide incorporation by mammalian DNA polymerase delta. J Biol Chem. 2000;275:16316-22 pubmed..PCNA appears to affect pol delta replication in this model mainly by decreasing the dissociation of the polymerase from the DNA. ..
- Fiala K, Suo Z. Pre-steady-state kinetic studies of the fidelity of Sulfolobus solfataricus P2 DNA polymerase IV. Biochemistry. 2004;43:2106-15 pubmed..The mismatch incorporation rates, regardless of the 5'-template base, were approximately 2-3 orders of magnitude slower than the incorporation rates for matched nucleotides, which is the predominant contribution to the fidelity of Dpo4. ..
- Cramer J, Restle T. Pre-steady-state kinetic characterization of the DinB homologue DNA polymerase of Sulfolobus solfataricus. J Biol Chem. 2005;280:40552-8 pubmed..Thus, unlike replicative polymerases, an "induced fit" mechanism to select and incorporate nucleotides during DNA polymerization could not be detected for Dbh. ..
- Zang H, Irimia A, Choi J, Angel K, Loukachevitch L, Egli M, et al. Efficient and high fidelity incorporation of dCTP opposite 7,8-dihydro-8-oxodeoxyguanosine by Sulfolobus solfataricus DNA polymerase Dpo4. J Biol Chem. 2006;281:2358-72 pubmed..With dGTP placed opposite 8-oxoG, pairing was not to the 8-oxoG but to the 5' C (and in classic Watson-Crick geometry), consistent with the low frequency of this frameshift event observed in the catalytic assays. ..
- Nair D, Johnson R, Prakash L, Prakash S, Aggarwal A. Rev1 employs a novel mechanism of DNA synthesis using a protein template. Science. 2005;309:2219-22 pubmed..This mechanism provides an elegant means for promoting proficient and error-free synthesis through N2-adducted guanines that obstruct replication. ..
- Wang L, Broyde S. A new anti conformation for N-(deoxyguanosin-8-yl)-2-acetylaminofluorene (AAF-dG) allows Watson-Crick pairing in the Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4). Nucleic Acids Res. 2006;34:785-95 pubmed..Possible relevance of our new major groove structure for AAF-dG to other polymerases, lesion repair and solution conformations are discussed. ..
- Gu J, Xie Y, Schaefer H. Electron attachment to DNA single strands: gas phase and aqueous solution. Nucleic Acids Res. 2007;35:5165-72 pubmed..Thus the base-centered radical anions of the pyrimidine nucleotides might be the possible intermediates for DNA single-strand breakage. ..
- Lahoud G, Timoshchuk V, LEBEDEV A, de Vega M, Salas M, Arar K, et al. Enzymatic synthesis of structure-free DNA with pseudo-complementary properties. Nucleic Acids Res. 2008;36:3409-19 pubmed publisher..Further optimization and characterization of the synthesis and properties of pseudo-complementary DNA should lead to an ideal target for use with oligonucleotide probes that are <25 nt in length. ..
- Austin W, Armijo A, Campbell D, Singh A, Hsieh T, Nathanson D, et al. Nucleoside salvage pathway kinases regulate hematopoiesis by linking nucleotide metabolism with replication stress. J Exp Med. 2012;209:2215-28 pubmed publisher..This new model may be exploited therapeutically to induce synthetic sickness/lethality in hematological malignancies, and possibly in other cancers. ..
- Grant S, Bhalla K, McCrady C. Effect of tetrahydrouridine and deoxytetrahydrouridine on the interaction between 2'-deoxycytidine and 1-beta-D-arabinofuranosylcytosine in human leukemia cells. Leuk Res. 1991;15:205-13 pubmed
- Louat T, Servant L, Rols M, Bieth A, Teissie J, Hoffmann J, et al. Antitumor activity of 2',3'-dideoxycytidine nucleotide analog against tumors up-regulating DNA polymerase beta. Mol Pharmacol. 2001;60:553-8 pubmed..Therefore, the use of chain terminator anticancer agents could be suitable for the treatment of tumors with a high level of Pol beta. ..
- Wang Y, Reddy S, Beard W, Wilson S, Schlick T. Differing conformational pathways before and after chemistry for insertion of dATP versus dCTP opposite 8-oxoG in DNA polymerase beta. Biophys J. 2007;92:3063-70 pubmed
- Kellerman D, Rossi Mospan A, Engels J, Schaberg A, Gorden J, Smiley L. Denufosol: a review of studies with inhaled P2Y(2) agonists that led to Phase 3. Pulm Pharmacol Ther. 2008;21:600-7 pubmed publisher..The first Phase 3 trial is a comparison of denufosol 60mg and placebo in 350 patients with CF with FEV1 at study entry greater than or equal to 75% of predicted. ..
- Richardson F, Kuchta R, Mazurkiewicz A, Richardson K. Polymerization of 2'-fluoro- and 2'-O-methyl-dNTPs by human DNA polymerase alpha, polymerase gamma, and primase. Biochem Pharmacol. 2000;59:1045-52 pubmed..The current studies showed that human polymerases can polymerize numerous 2'-FdNTPs but cannot polymerize 2'-O-MedNTPs. ..
- van Wijk G, Hostetler K, Schlame M, van den Bosch H. Cytidine diphosphate diglyceride analogs of antiretroviral dideoxynucleosides: evidence for release of dideoxynucleoside-monophosphates by phospholipid biosynthetic enzymes in rat liver subcellular fractions. Biochim Biophys Acta. 1991;1086:99-105 pubmed
- Huang P, Chubb S, Hertel L, Grindey G, Plunkett W. Action of 2',2'-difluorodeoxycytidine on DNA synthesis. Cancer Res. 1991;51:6110-7 pubmed..Our results demonstrate qualitative and quantitative differences in the molecular actions of dFdC and arabinosylcytosine on DNA metabolism, but are consistent with an important role for such incorporation in the toxicity of dFdC. ..
- Yang L, Li L, Jiang H, Shen Y, Plunkett W. Expression of ERCC1 antisense RNA abrogates gemicitabine-mediated cytotoxic synergism with cisplatin in human colon tumor cells defective in mismatch repair but proficient in nucleotide excision repair. Clin Cancer Res. 2000;6:773-81 pubmed..These data provide direct evidence to support the hypothesis that inhibition of the repair of CDDP-induced DNA lesions plays a critical role in dFdC-mediated cytotoxic synergism with CDDP in MMR-deficient tumor cells. ..
- Zhuang P, Kolbanovskiy A, Amin S, Geacintov N. Base sequence dependence of in vitro translesional DNA replication past a bulky lesion catalyzed by the exo- Klenow fragment of Pol I. Biochemistry. 2001;40:6660-9 pubmed..The latter depend on the base Y and on the base preferentially inserted opposite the adduct. Thus, downstream template sequences as well as the bases flanking G* influence DNA translesion synthesis. ..
- Ge J, Yu G, Ator M, Stubbe J. Pre-steady-state and steady-state kinetic analysis of E. coli class I ribonucleotide reductase. Biochemistry. 2003;42:10071-83 pubmed
- Dobrikov M, Grady K, Shaw B. Introduction of the alpha-P-borano-group into deoxynucleoside triphosphates increases their selectivity to HIV-1 reverse transcriptase relative to DNA polymerases. Nucleosides Nucleotides Nucleic Acids. 2003;22:275-82 pubmed..Thus, introduction of the alpha-boranophosphate group into dNTPs increases their selectivity to HIV-1 RT relative to bacterial DNA polymerases. ..
- Aduma P, Gupta S, Stuart A, Tourigny G. Deoxyribonucleoside triphosphate pools of herpes simplex virus infected cells: the influence of selective antiherpes agents and the role of the deaminase pathway. Biochem Cell Biol. 1991;69:409-14 pubmed..These results indicate that during viral replication the bulk of the thymidine nucleotides are derived from the dCyd/dCMP deaminase de novo pathway. ..
- Kocic G, Pavlovic V, Saranac L, Kocic R, Zivic S, Sokolovic D, et al. Circulating nucleic acids in type 1 diabetes may modulate the thymocyte turnover rate. Cell Immunol. 2010;266:76-82 pubmed publisher..The dysregulation of inflammatory cascade and central tolerance may be a defect in autoimmune diseases related to innate immunity leading to corresponding alteration in adaptive immune response. ..
- Xia Z, Azurmendi H, Mildvan A. Transient state kinetic studies of the MutT-catalyzed nucleoside triphosphate pyrophosphohydrolase reaction. Biochemistry. 2005;44:15334-44 pubmed..5 nM for 8-oxo-dGTP and 62 microM for dGTP, indicating that 8-oxo-dGTP binds 1.8 x 10(4)-fold tighter than dGTP, corresponding to a 5.8 kcal/mol lower free energy of binding. ..
- Feng J, Murakami E, Zorca S, Johnson A, Johnson K, Schinazi R, et al. Relationship between antiviral activity and host toxicity: comparison of the incorporation efficiencies of 2',3'-dideoxy-5-fluoro-3'-thiacytidine-triphosphate analogs by human immunodeficiency virus type 1 reverse transcriptase and human mitochondria. Antimicrob Agents Chemother. 2004;48:1300-6 pubmed..6-fold slower than the excision of dCMP. These results demonstrate that there are clear differences between HIV-1 RT and polymerase gamma in terms of preferences for substrate structure. ..
- Fagny C, Vandevelde M, Svoboda M, Robberecht P. Ribonucleotide reductase and thymidine phosphorylation: two potential targets of azodicarbonamide. Biochem Pharmacol. 2002;64:451-6 pubmed..This effect was not reproduced by hydroxyurea. Thus, in vitro azodicarbonamide decreases the intracellular pool of deoxyribonucleotide and thymidine phosphorylation. ..
- Jang J, Kim S, Yoon B, Ryu J, Gu M, Chang H. Detection of Alicyclobacillus species in fruit juice using a random genomic DNA microarray chip. J Food Prot. 2011;74:933-8 pubmed publisher..This microarray system is a good tool for rapid and specific detection of thermophilic spoilage bacteria, mainly Alicyclobacillus spp., and is useful and applicable to the fruit juice industry. ..
- Allard P, Kuprin S, Shen B, Ehrenberg A. Binding of the competitive inhibitor dCDP to ribonucleoside-diphosphate reductase from Escherichia coli studied by 1H NMR. Different properties of the large protein subunit and the holoenzyme. Eur J Biochem. 1992;208:635-42 pubmed..5. The effect of R2 without iron (apoR2) is reduced compared with native R2, probably because of some denatured proteins, while a C-terminal peptide from R2 did not cause any narrowing at all. ..
- Bauer W, Horvath Z, Höchtl T, Saiko P, Karl D, Fritzer Szekeres M, et al. Amidox, an inhibitor of ribonucleotide reductase, potentiates the action of Ara-C in HL-60 human promyelocytic leukemia cells. Nucleosides Nucleotides Nucleic Acids. 2004;23:1541-4 pubmed..In conclusion, Amidox might offer an additional option for the treatment of leukemia and thus be further investigated in vitro and in vivo. ..
- Accurso F, Moss R, Wilmott R, Anbar R, Schaberg A, Durham T, et al. Denufosol tetrasodium in patients with cystic fibrosis and normal to mildly impaired lung function. Am J Respir Crit Care Med. 2011;183:627-34 pubmed publisher..Denufosol improved lung function relative to placebo in cystic fibrosis patients with normal to mildly impaired lung function. Clinical trial registered with www.clinicaltrials.gov (NCT00357279). ..
- Makeyev E, Bamford D. Primer-independent RNA sequencing with bacteriophage phi6 RNA polymerase and chain terminators. RNA. 2001;7:774-81 pubmed..Furthermore, using genomic segments of the bluetongue virus we show that RdRP sequencing can also be applied to naturally occurring dsRNA templates. This suggests possible uses of the method in the RNA virus research and diagnostics...
- Bouffard D, Laliberte J, Momparler R. Kinetic studies on 2',2'-difluorodeoxycytidine (Gemcitabine) with purified human deoxycytidine kinase and cytidine deaminase. Biochem Pharmacol. 1993;45:1857-61 pubmed..Inhibitors of CDA could be useful in clinical trials in patients with cancer to increase the chemotherapeutic effectiveness of dFdC. ..
- Swart J, Griep M. Primer synthesis kinetics by Escherichia coli primase on single-stranded DNA templates. Biochemistry. 1995;34:16097-106 pubmed..Nevertheless, the overlong primers did appear to arise as a consequence of the template length-dependent species since their length was double and they arose in the time course after the length-dependent species. ..
- Jia L, Geacintov N, Broyde S. The N-clasp of human DNA polymerase kappa promotes blockage or error-free bypass of adenine- or guanine-benzo[a]pyrenyl lesions. Nucleic Acids Res. 2008;36:6571-84 pubmed publisher..Absence of the N-clasp in Dpo4 explains the error-prone processing of the same lesion by this enzyme. Thus, our studies elucidate structure-function relationships in the fidelity of lesion bypass. ..
- Zhang H, Guengerich F. Effect of N2-guanyl modifications on early steps in catalysis of polymerization by Sulfolobus solfataricus P2 DNA polymerase Dpo4 T239W. J Mol Biol. 2010;395:1007-18 pubmed publisher..With the larger adducts (>or=(2-naphthyl)methyl), the absence of fluorescence changes suggests impaired ability to undergo an appropriate conformational change, consistent with previous structural work...
- Button B, Okada S, Frederick C, Thelin W, Boucher R. Mechanosensitive ATP release maintains proper mucus hydration of airways. Sci Signal. 2013;6:ra46 pubmed publisher..Understanding how airway epithelia can sense and respond to changes in mucus properties helps us to understand how the mucus clearance system protects the airways in health and how it fails in lung diseases such as cystic fibrosis. ..
- Evans F, Levine R. NMR study of stacking interactions and conformational adjustments in the dinucleotide-carcinogen adduct 2'-deoxycytidylyl-(3----5)-2'-deoxy-8-(N-fluoren-2-ylac etamido)guanosi ne. Biochemistry. 1988;27:3046-55 pubmed..Such structures could explain the relatively rapid rate of repair and the frame-shift mutations of this type of adduct. ..
- Deterding R, Retsch Bogart G, Milgram L, Gibson R, Daines C, Zeitlin P, et al. Safety and tolerability of denufosol tetrasodium inhalation solution, a novel P2Y2 receptor agonist: results of a phase 1/phase 2 multicenter study in mild to moderate cystic fibrosis. Pediatr Pulmonol. 2005;39:339-48 pubmed..recently completed a multicenter, 28-day, phase 2 safety and efficacy clinical trial of denufosol inhalation solution in CF subjects with mild lung disease. ..
- Yerxa B, Douglass J, Elena P, Caillaud T, Amar T, Edick C, et al. Potency and duration of action of synthetic P2Y2 receptor agonists on Schirmer scores in rabbits. Adv Exp Med Biol. 2002;506:261-5 pubmed
- Fernandes P, Ramos M. Theoretical studies on the mechanism of inhibition of Ribonucleotide Reductase by (E)-2'-Fluoromethylene-2'-deoxycitidine-5'-diphosphate. J Am Chem Soc. 2003;125:6311-22 pubmed..It is shown also that the major mode of inactivation mimics the early stages of the natural substrate pathway. ..
- Wang F. Unsaturated didehydrodeoxycytidine drugs. 1. Impact of C=C positions in the sugar ring. J Phys Chem B. 2007;111:9628-33 pubmed..Finally, the present study suggests that the nearly 0.6 eV difference in the first ionization potentials (highest occupied molecular orbital) of the isomers is sufficiently large to identify them by further spectroscopic measures. ..
- Cockrell G, Kantrowitz E. Metal ion involvement in the allosteric mechanism of Escherichia coli aspartate transcarbamoylase. Biochemistry. 2012;51:7128-37 pubmed..These results also call into question many of the past kinetic and binding experiments with ATCase with nucleotides as the presence of metal contamination was not considered important. ..