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| deoxyribonucleotidesSummarySummary: A purine or pyrimidine base bonded to a DEOXYRIBOSE containing a bond to a phosphate group. Top Publications
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Highly mutagenic and severely imbalanced dNTP pools can escape detection by the S-phase checkpointDinesh Kumar
Department of Medical Biochemistry and Biophysics, Umea University, SE 90187 Umea, Sweden
Nucleic Acids Res 38:3975-83. 2010..In contrast, when none of the dNTPs was limiting for DNA replication, even extreme and mutagenic dNTP pool imbalances did not activate the S-phase checkpoint and did not interfere with the cell cycle progression...
Regulation of mammalian ribonucleotide reduction and dNTP pools after DNA damage and in resting cellsPelle Håkansson
Department of Medical Biochemistry and Biophysics, Umea University, SE 90187 Umea, Sweden
J Biol Chem 281:7834-41. 2006....
Mitochondrial deoxynucleotide pools in quiescent fibroblasts: a possible model for mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)Paola Ferraro
Department of Biology, The University of Padova, 35131 Padova, Italy
J Biol Chem 280:24472-80. 2005..Other dNTPs are marginally affected. Deoxyuridine does not increase the normal dNTP pools but gives rise to a small dUTP and a large dUMP pool, both turning over rapidly. We discuss these results in relation to MNGIE...
Impaired function of p53R2 in Rrm2b-null mice causes severe renal failure through attenuation of dNTP poolsTakashi Kimura
Human Genome Center, Institute of Medical Science, University of Tokyo, 4 6 1 Shirokanedai, Minato ku, Tokyo 108 8639, Japan
Nat Genet 34:440-5. 2003..To determine whether it is involved in DNA repair by supplying deoxyribonucleotides (dNTPs) for resting cells in vivo, we generated a strain of mice lacking Rrm2b (encoding p53R2)...
Manganese substantially alters the dynamics of translesion DNA synthesisHeather Hays
Department of Chemistry, Case Western Reserve University, 2109 Adelbert Road, Cleveland, Ohio 44106, USA
Biochemistry 41:4771-8. 2002..Various models are discussed in an attempt to explain the effect of metal ion substitution on the dynamics of translesion DNA replication...
Is a thymine dimer replicated via a transient abasic site intermediate? A comparative study using non-natural nucleotidesBabho Devadoss
Department of Chemistry, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA
Biochemistry 46:4486-98. 2007..The data for both nucleotide incorporation and excision are used to propose models accounting for polymerase "switching" during translesion DNA synthesis...
Ribonucleotide reductase is not limiting for mitochondrial DNA copy number in miceEmil Ylikallio
Biomedicum Helsinki, Research Programme of Molecular Neurology, University of Helsinki, Haartmaninkatu 8, PO Box 63, 00290 Helsinki, Finland
Nucleic Acids Res 38:8208-18. 2010..Our results establish that RNR is not limiting for mtDNA copy number in mice, and provide new evidence for the importance of balanced dNTP pools in mtDNA maintenance in postmitotic tissues...
Deoxyribonucleotide pool imbalance stimulates deletions in HeLa cell mitochondrial DNAShiwei Song
Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregeon 97331-7305, USA
J Biol Chem 278:43893-6. 2003..Our finding of dTTP and dGTP elevations and dATP depletion in mitochondrial dNTP pools are consistent with a mutagenic mechanism involving T-G mispairing followed by a next-nucleotide effect involving T insertion opposite A...
An error-prone family Y DNA polymerase (DinB homolog from Sulfolobus solfataricus) uses a 'steric gate' residue for discrimination against ribonucleotidesAngela M DeLucia
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA
Nucleic Acids Res 31:4129-37. 2003..When making a deletion error, ribonucleotide discrimination by wild-type and F12A Dbh is the same as in normal DNA synthesis, indicating that the geometry of nucleotide binding is similar in both circumstances...
Regulation by degradation, a cellular defense against deoxyribonucleotide pool imbalancesChiara Rampazzo
Department of Biology, University of Padova, Via Ugo Bassi 58B, 35131 Padova, Italy
Mutat Res 703:2-10. 2010..The role of some relevant enzymes is illustrated with data obtained by chemical or genetic manipulation of their expression in cultured mammalian cells...
Quantitation of cellular deoxynucleoside triphosphatesPaola Ferraro
Department of Biology, University of Padova, 35131 Padova, Italy
Nucleic Acids Res 38:e85. 2010..We suggest that in some earlier reports ribonucleotide incorporation may have caused too high values for dGTP and dCTP...
A system for rapid DNA sequencing with fluorescent chain-terminating dideoxynucleotidesJ M Prober
Engineering Physics Laboratory, E I du Pont de Nemours and Company Inc, Wilmington, DE 19898
Science 238:336-41. 1987..A scanning system allows multiple samples to be run simultaneously and computer-based automatic base sequence identifications to be made. The sequence analysis of M13 phage DNA made with this system is described...
Stable suppression of the R2 subunit of ribonucleotide reductase by R2-targeted short interference RNA sensitizes p53(-/-) HCT-116 colon cancer cells to DNA-damaging agents and ribonucleotide reductase inhibitorsZ Ping Lin
Department of Pharmacology and Cancer Center, Yale University School of Medicine, New Haven, Connecticut 06520, USA
J Biol Chem 279:27030-8. 2004..The findings provide evidence that R2-RNR can be employed to supply dNTPs for the repair of DNA damage in cells with an impaired p53-dependent induction of p53R2...
Evaluating the contributions of desolvation and base-stacking during translesion DNA synthesisXuemei Zhang
Department of Pharmacology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA
Org Biomol Chem 2:1703-11. 2004..This result indicates that indolyl-2'-deoxyriboside triphosphate acts as an indiscriminate chain terminator of DNA synthesis that may have unique therapeutic applications...
A novel homozygous RRM2B missense mutation in association with severe mtDNA depletionGittan Kollberg
Department of Clinical Chemistry, Sahlgrenska University Hospital, Bruna Straket 16, SE 413 45 Goteborg, Sweden
Neuromuscul Disord 19:147-50. 2009..This is the third report on mutations in RRM2B associated with severe mtDNA depletion, which further highlights the importance of de novo synthesis of deoxyribonucleotides (dNTPs) for mtDNA maintenance.
Interference of gemcitabine triphosphate with the measurements of deoxynucleotides using an optimized DNA polymerase elongation assayK Smid
Department of Medical Oncology, Vrije Universiteit Medical Centre (VUMC, PO Box 7057, 1007 MB Amsterdam, The Netherlands
Int J Oncol 19:157-62. 2001..In conclusion, dFdCTP affects dNTP measurements with the DNA polymerase elongation assay, but its effect could be controlled by addition of similar amounts of dFdCTP to each assay...
Simultaneous determination of pyrimidine or purine deoxyribonucleoside triphosphates using a polymerase assayB Roy
Institut de Biochemie Biophysique Cellulaire et Moléculaire Unité CNRS 571, Universite Paris Sud, Orsay, France
Anal Biochem 269:403-9. 1999..Furthermore, this new protocol is well suited for the determination of dNTPs in cells treated with the antiretroviral ddI, since the Klenow fragment has a low affinity for ddATP, the active form of ddI...
Evaluating the contribution of base stacking during translesion DNA replicationEdmunds Z Reineks
Department of Pharmacology and the Comprehensive Cancer Center, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA
Biochemistry 43:393-404. 2004..These kinetic differences are interpreted with regard to the differences in various structural components between the two enzymes and are consistent with the proposed model for DNA polymerization...
Mitochondrial deoxyribonucleotide pools in deoxyguanosine kinase deficiencyAnn Saada
Metabolic Disease Unit, Hadassah Medical Center, Jerusalem 91120, Israel
Mol Genet Metab 95:169-73. 2008..It is suggested that the cytoplasmic deoxycytine kinase supplemented with external substrates may compensate for the deficient dGK...
Thymidine kinase 2 (H126N) knockin mice show the essential role of balanced deoxynucleotide pools for mitochondrial DNA maintenanceHasan O Akman
Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
Hum Mol Genet 17:2433-40. 2008..The H126N TK2 mouse is the first knock-in animal model of human MDS and demonstrates that the severity of TK2 deficiency in tissues may determine the organ-specific phenotype...
Efficient and accurate replication in the presence of 7,8-dihydro-8-oxoguanine by DNA polymerase etaL Haracska
Sealy Center for Molecular Science, University of Texas Medical Branch at Galveston, Galveston, Texas, USA
Nat Genet 25:458-61. 2000..Our results suggest an additional role for Poleta in the prevention of internal cancers in humans that would otherwise result from the mutagenic replication of 8-oxoG in DNA...
Genetic and chemical rescue of the Saccharomyces cerevisiae phenotype induced by mitochondrial DNA polymerase mutations associated with progressive external ophthalmoplegia in humansEnrico Baruffini
Department of Genetics, Biology of Microorganisms, Anthropology, Evolution, University of Parma, Italy
Hum Mol Genet 15:2846-55. 2006..Therefore, an increase of the mitochondrial dNTP pool and/or a decrease of reactive oxygen species can prevent the mtDNA damage induced by pol gamma mutations in yeast and, possibly, in humans...
Substrate specificity of vaccinia virus thymidylate kinaseDimitri Topalis
, FRE 2852 CNRS, Paris, France
FEBS J 272:6254-65. 2005..Several thymidine and dTMP derivatives were found to bind the enzyme with micromolar affinities. The present study provides the basis for the design of specific inhibitors or substrates for poxvirus TMP kinase...
Abasic DNA structure, reactivity, and recognitionJ Lhomme
LEDSS, Chimie Bioorganique, UMR CNRS 5616, Universite Joseph Fourier, Grenoble Cedex 9, France
Biopolymers 52:65-83. 1999..Others have been prepared that bind strongly to the abasic site and show promise in potentiating the cytotoxic and antitumor activity of the clinically used nitrosourea (bis-chloroethylnitrosurea)...
Terminal deoxynucleotidyl transferase indiscriminately incorporates ribonucleotides and deoxyribonucleotidesJ B Boulé
Unité de Génétique et Biochimie du Développement, URA CNRS 1960, Institut Pasteur, 25 rue du Dr Roux, 75015 Paris, France
J Biol Chem 276:31388-93. 2001Terminal deoxynucleotidyl transferase (TdT) catalyzes the condensation of deoxyribonucleotides on 3'-hydroxyl ends of DNA strands in a template-independent manner and adds N-regions to gene segment junctions during V(D)J recombination...
Lack of sugar discrimination by human Pol mu requires a single glycine residueJose F Ruiz
Centro de Biologia Molecular Severo Ochoa CSIC UAM, Campus de la Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid, Spain
Nucleic Acids Res 31:4441-9. 2003..The unusual capacity to insert both rNTPs and dNTPs will be discussed in the context of the predicted roles of Pol mu in DNA repair...
Incorporation of reporter molecule-labeled nucleotides by DNA polymerases. II. High-density labeling of natural DNATaurai Tasara
Gnothis SA, PSE-B, EPFL, CH-1015 Lausanne, Switzerland
Nucleic Acids Res 31:2636-46. 2003..Moreover, we present systematic testing of various combinations of fluorescent dye-modified dNTPs enabling the simultaneous labeling of DNA with up to four differently modified dNTPs...
Structural basis for allosteric substrate specificity regulation in anaerobic ribonucleotide reductasesK M Larsson
Department of Biochemistry and Biophysics, Stockholm University, S-106 91, Stockholm, Sweden
Structure 9:739-50. 2001..We propose that the altered overlap of Phe-194 with the substrate base governs hydrogen bonding patterns with main and side chain hydrogen bonding groups in the active site. The relevance for evolution is discussed...
Guanine nucleosides and Jurkat cell death: roles of ATP depletion and accumulation of deoxyribonucleotidesT D Batiuk
Department of Medicine, Indiana University and Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana 46202, USA
Am J Physiol Cell Physiol 281:C1776-84. 2001..In conclusion, guanosine and deoxyguanosine are toxic to Jurkat cells through two mechanisms: ATP depletion, causing necrosis, and the accumulation of dGTP, resulting in apoptosis...
Use of viscogens, dNTPalphaS, and rhodium(III) as probes in stopped-flow experiments to obtain new evidence for the mechanism of catalysis by DNA polymerase betaMarina Bakhtina
Department of Chemistry and Biochemistry and Ohio State Biochemistry Program, The Ohio State University, Columbus, Ohio 43210, USA
Biochemistry 44:5177-87. 2005..The methodologies can be used to examine other DNA polymerases to answer whether the properties of Pol beta are exceptional or general...
Mitochondrial deoxyribonucleotides, pool sizes, synthesis, and regulationChiara Rampazzo
Department of Biology, University of Padova, I-35131 Padova, Italy
J Biol Chem 279:17019-26. 2004..These results suggest that mdN modulates the synthesis of mt dTTP by counteracting in a substrate cycle the phosphorylation of thymidine by the mt thymidine kinase...
Polymerase mu is a DNA-directed DNA/RNA polymeraseStephanie A Nick McElhinny
Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
Mol Cell Biol 23:2309-15. 2003....
Determination of DNA structure in solution: enzymatic deuteration of the ribose 2' carbonDouglas Macdonald
Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6323, USA
J Am Chem Soc 124:9722-3. 2002..As an example, these labeled nucleotides are incorporated uniquely at positions 6-14 in a 20-bp DNA sequence containing the adenovirus major late promoter...
Variants of DNA polymerase Beta extend mispaired DNA due to increased affinity for nucleotide substrateAmit M Shah
Yale University School of Medicine, Departments of Therapeutic Radiology and Genetics, New Haven, Connecticut 06520, USA
Biochemistry 42:10709-17. 2003....
Pre-steady-state kinetic studies of the fidelity of human DNA polymerase muMichelle P Roettger
Department of Biochemistry, Ohio State Biochemistry Program, The Ohio State University, Columbus, Ohio 43210, USA
Biochemistry 43:13827-38. 2004..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...
Use of 2-aminopurine fluorescence to examine conformational changes during nucleotide incorporation by DNA polymerase I (Klenow fragment)Vandana Purohit
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA
Biochemistry 42:10200-11. 2003....
Incorporation of reporter molecule-labeled nucleotides by DNA polymerases. I. Chemical synthesis of various reporter group-labeled 2'-deoxyribonucleoside-5'-triphosphatesGerald Giller
Gnothis SA, PSE-B, EPFL, CH-1015 Lausanne, , D-82398 Polling, Germany
Nucleic Acids Res 31:2630-5. 2003..Our data suggest that the incorporation efficiency depends on the selected dye, the nucleobase or a combination of both...
Deoxyribonucleotides and disorders of mitochondrial DNA integrityAnn Saada
Metabolic Disease Unit, Shaare Zedek Medical Center, Jerusalem, Israel
DNA Cell Biol 23:797-806. 2004..This article reviews the current knowledge of deoxyribonucleotide metabolism in relation to disorders affecting mtDNA integrity...
DNA precursor asymmetries in mammalian tissue mitochondria and possible contribution to mutagenesis through reduced replication fidelityShiwei Song
Department of Biochemistry and Biophysics, Oregon State University, 2011 ALS, Corvallis, OR 97331 7305, USA
Proc Natl Acad Sci U S A 102:4990-5. 2005....
Erroneous incorporation of oxidized DNA precursors by Y-family DNA polymerasesMasatomi Shimizu
Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan
EMBO Rep 4:269-73. 2003..We also report that human DNA polymerase eta, a human Y-family DNA polymerase, incorporates the oxidized dNTPs in a similar erroneous manner...
SNP genotyping using alkali cleavage of RNA/DNA chimeras and MALDI time-of-flight mass spectrometryFlorence Mauger
, , 91057 Evry Cedex, France
Nucleic Acids Res 34:e18. 2006....
How E. coli DNA polymerase I (Klenow fragment) distinguishes between deoxy- and dideoxynucleotidesM Astatke
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, 06520, USA
J Mol Biol 278:147-65. 1998....
Use of damaged DNA and dNTP substrates by the error-prone DNA polymerase X from African swine fever virusSandeep Kumar
Department of Chemistry, The Biophysics Program, The Ohio State University, Columbus, Ohio 43210, USA
Biochemistry 46:3814-25. 2007..Our findings are discussed in light of ASFV biology and the mutagenic DNA repair hypothesis described above...
Fidelity of mutant HIV-1 reverse transcriptases: interaction with the single-stranded template influences the accuracy of DNA synthesisB Kim
The Joseph Gottstein Memorial Cancer Research Laboratory, Department of Pathology, University of Washington, Seattle 98195 3577, USA
Biochemistry 37:5831-9. 1998....
Mismatched dNTP incorporation by DNA polymerase beta does not proceed via globally different conformational pathwaysKuo Hsiang Tang
Departments of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA
Nucleic Acids Res 36:2948-57. 2008....
Maintaining precursor pools for mitochondrial DNA replicationChristopher K Mathews
Department of Biochemistry and Biophysics, Oregon State University, 2011 Agricultural and Life Sciences Bldg, Corvallis, OR 97331 7305, USA
FASEB J 21:2294-303. 2007..These factors suggest that much more information is needed about maintenance and regulation of dNTP pools within mammalian mitochondria. This review summarizes our current understanding and suggests directions for future research...
Crystal structures of the Klenow fragment of DNA polymerase I complexed with deoxynucleoside triphosphate and pyrophosphateL S Beese
Department of Molecular Biophysics, Yale University, New Haven, Connecticut 06511
Biochemistry 32:14095-101. 1993..M. (1992) J. Biol. Chem. 267, 8417-8428]. However, we conclude that the position of at least the dNMP moiety of dNTP in the binary complex is not likely to be the same as in its catalytically relevant complex with primer-template DNA...
Unbalanced deoxynucleotide pools cause mitochondrial DNA instability in thymidine phosphorylase-deficient miceLuis C Lopez
Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
Hum Mol Genet 18:714-22. 2009..These findings largely account for the pathogenesis of mitochondrial neurogastrointestinal encephalopathy (MNGIE), the first inherited human disorder of nucleoside metabolism associated with somatic DNA instability...
Crystal structures of human DNA polymerase beta complexed with DNA: implications for catalytic mechanism, processivity, and fidelityH Pelletier
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla 92093 0506, USA
Biochemistry 35:12742-61. 1996..A model for productive binding of pol beta to a gapped-DNA substrate requires a 90 degrees bend in the single-stranded template, which could enhance nucleotide selectivity during DNA repair or replication...
UvrA and UvrB enhance mutations induced by oxidized deoxyribonucleotidesMika Hori
Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita ku, Sapporo 060 0812, Japan
DNA Repair (Amst) 6:1786-93. 2007Oxidatively damaged DNA precursors (deoxyribonucleotides) are formed by reactive oxygen species. After the damaged DNA precursors are incorporated into DNA, they might be removed by DNA repair enzymes...
Enantioselectivity of human AMP, dTMP and UMP-CMP kinasesJulie A C Alexandre
Laboratoire d Enzymologie Moleculaire, FRE 2852 CNRS Université Paris 6, 4, place Jussieu, 75005 Paris, France
Nucleic Acids Res 35:4895-904. 2007..This in vitro information was then used to develop the in vivo activation pathway for L-dT...
Inhibition of ribozymes by deoxyribonucleotides and the origin of DNAP E Leon
School of Medicine and Cell and Molecular Biology Research Center CIBCM, Universidad de Costa Rica, San Jose, Costa Rica
J Mol Evol 47:122-6. 1998..DNA was useless as template until a transcriptase (DNA-dependent RNA polymerase) evolved that could copy (-)DNA to reconstitute the (+)RNA genome, indeed a successful way of confronting ribonuclease threats in the RNA world...
Defects in maintenance of mitochondrial DNA are associated with intramitochondrial nucleotide imbalancesNeil Ashley
Mitochondrial Genetics Group, Nuffield Department of Obstetrics and Gynaecology, Level 3, Women s Centre, The John Radcliffe Hospital, Oxford OX3 9DU, UK
Hum Mol Genet 16:1400-11. 2007..Because deviations from the normal concentrations of dNTPs are known to be mutagenic, we suggest that intramitochondrial nucleotide imbalance could underlie the multiple mtDNA mutations observed in these patients...
Structures of eukaryotic ribonucleotide reductase I provide insights into dNTP regulationHai Xu
Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, M407 Walters Life Sciences, Knoxville, TN 37996 0840, USA
Proc Natl Acad Sci U S A 103:4022-7. 2006..Finally, the substrate ribose binds with its 3' hydroxyl closer than its 2' hydroxyl to C218 of the catalytic redox pair. We also see a conserved water molecule at the catalytic site in all our structures, near the ribose 2' hydroxyl...
Mutagenic nucleotide incorporation and hindered translocation by a food carcinogen C8-dG adduct in Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4): modeling and dynamics studiesLing Zhang
Department of Chemistry, New York University, New York, NY, USA
Nucleic Acids Res 34:3326-37. 2006..2006), PLoS Biol., 4, e11). However, N2-dG adducts, which can reside on the minor groove side, appear to cause less hindrance when in this position...
Evidence for lesion bypass by yeast replicative DNA polymerases during DNA damageNasim Sabouri
Department of Medical Biochemistry and Biophysics, Umea University, SE 901 87 Umea, Sweden
Nucleic Acids Res 36:5660-7. 2008The enzyme ribonucleotide reductase, responsible for the synthesis of deoxyribonucleotides (dNTP), is upregulated in response to DNA damage in all organisms...
Deoxyribonucleotides are maintained at normal levels in a yeast thioredoxin mutant defective in DNA synthesisE G Muller
Department of Biochemistry, University of Washington, Seattle 98195
J Biol Chem 269:24466-71. 1994..The second proposes that thioredoxin regulates the tempo of DNA replication directly by activating a component of the replication machinery...
Efficient bypass of a thymine-thymine dimer by yeast DNA polymerase, PoletaR E Johnson
Sealy Center for Molecular Science, University of Texas Medical Branch at Galveston, 6 104 Medical Research Building, 11th and Mechanic Streets, Galveston, TX 77555 1061, USA
Science 283:1001-4. 1999..When incubated in vitro with all four nucleotides, Rad30 incorporates two adenines opposite the thymine-thymine dimer. Rad30 is the seventh eukaryotic DNA polymerase to be described and hence is named DNA polymerase eta...
A suppressor of two essential checkpoint genes identifies a novel protein that negatively affects dNTP poolsX Zhao
Department of Genetics and Development, Columbia University, College of Physicians and Surgeons, New York, New York 10032 2704, USA
Mol Cell 2:329-40. 1998..Finally, both in vivo and in vitro experiments show that Sml1 binds to Rnr1. We propose that Sml1 inhibits dNTP synthesis posttranslationally by binding directly to Rnr1 and that Mec1 and Rad53 are required to relieve this inhibition...
Substrate specificity and phosphorylation of antiviral and anticancer nucleoside analogues by human deoxyribonucleoside kinases and ribonucleoside kinasesAn R Van Rompay
Department of Nephrology-Hypertension, University of Antwerp, 2610 Antwerp, Belgium
Pharmacol Ther 100:119-39. 2003..This overview is focused on the substrate specificity, tissue distribution, and subcellular location of the mammalian dNKs and rNKs and their role in the activation of NAs...
Pre-steady-state kinetic studies of protein-template-directed nucleotide incorporation by the yeast Rev1 proteinCraig A Howell
Department of Biochemistry, University of Iowa College of Medicine, Iowa City, Iowa 52242 1109, USA
Biochemistry 46:13451-9. 2007..Moreover, on the basis of these findings and on structures of the unrelated Escherichia coli MutM DNA glycosylase, we suggest the possible structures for the ternary complexes of Rev1p with the other incoming dNTPs...
Transfer RNA aminoacylation: identification of a critical ribose 2'-hydroxyl-base interactionL P Yap
Department of Chemistry, University of Minnesota, Minneapolis 55455, USA
RNA 1:418-24. 1995..This is the first study to identify a specific ribose 2'-hydroxyl-base interaction in the core region of a tRNA molecule that makes a thermodynamically significant contribution to aminoacylation...
Conformational changes during normal and error-prone incorporation of nucleotides by a Y-family DNA polymerase detected by 2-aminopurine fluorescenceAngela M DeLucia
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520 8114, USA
Biochemistry 46:10790-803. 2007....
A versatile toolbox for variable DNA functionalization at high densityStefan Jäger
Kekuké Institut für Organische Chemie und Biochemie, Universitat Bonn, Gerhard Domagk Strasse 1, D 53121 Bonn, Germany
J Am Chem Soc 127:15071-82. 2005..Our study provides a basis for establishing a generally applicable toolbox of enzymes, templates, and monomers for generating high-density functionalized DNAs for a broad range of applications...
Human DNA polymerase iota utilizes different nucleotide incorporation mechanisms dependent upon the template baseM Todd Washington
Sealy Center for Molecular Science, University of Texas Medical Branch at Galveston, 6 104 Blocker Medical Research Building, 11th and Mechanic Streets, Galveston, TX 77555 1061, USA
Mol Cell Biol 24:936-43. 2004....
Single-base discrimination mediated by proofreading 3' phosphorothioate-modified primersJia Zhang
Carroll Canyon Road, Apt. 47, San Diego, CA 92126, USA
Mol Biotechnol 25:223-8. 2003..This novel single-base discrimination method has potential in SNP assays...
The balance between the rates of incorporation and pyrophosphorolytic removal influences the HIV-1 reverse transcriptase bypass of an abasic site with deoxy-, dideoxy-, and ribonucleotidesBechan Sharma
Department of Biochemistry, University of Allahabad, Allahabad, India
Proteins 71:715-27. 2008..We find that AP sites can substantially influence the substrate specificity of HIV-1 RT and that pyrophosphorolysis plays a significant role in determining the ability of HIV-1 RT to (mis)incorporate nucleotides...
Abnormalities in uridine homeostatic regulation and pyrimidine nucleotide metabolism as a consequence of the deletion of the uridine phosphorylase geneDeliang Cao
Cancer Institute, Southern Illinois University School of Medicine, Springfield, Illinois 62702, USA
J Biol Chem 280:21169-75. 2005..These data indicate that UPase is a critical enzyme in the regulation of uridine homeostasis and pyrimidine nucleotide metabolism, and 5-fluorouracil activity...
Fluorescence of 2-aminopurine reveals rapid conformational changes in the RB69 DNA polymerase-primer/template complexes upon binding and incorporation of matched deoxynucleoside triphosphatesH Zhang
Department of Molecular Biophysics and Biochemistry, Yale University, 333 Cedar Street, New Haven, CT 06520, USA
Nucleic Acids Res 35:6052-62. 2007....
Sequence-specific cleavage of RNA in the absence of divalent metal ions by a DNAzyme incorporating imidazolyl and amino functionalitiesAlexander V Sidorov
Centre for Chemical Biology, Department of Chemistry, Krebs Institute, University of Sheffield, Sheffield S3 7HF, UK
Nucleic Acids Res 32:1591-601. 2004..The selected DNAzyme is two orders of magnitude more efficient in its cleavage of RNA than an unmodified DNAzyme in the absence of metal ions and represents a rate enhancement of 10(5) compared with the uncatalysed hydrolysis of RNA...
Dehydroleucodine inhibits vascular smooth muscle cell proliferation in G2 phaseM Cruzado
, , Mendoza, Argentina
Cell Mol Biol (Noisy-le-grand) 51:525-30. 2005..incorporation, and did not modify either the activity of DNA polymerase or the incorporation of deoxyribonucleotides in an in vitro assay. Moreover, DhL did not induce apoptosis in VSMCs...
3'-modified oligo (2'-O-methylribonucleotides) as improved probes for hybridization with RNAD S Novopashina
Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia
Nucleosides Nucleotides Nucleic Acids 24:527-31. 2005....
Stimulation of mutagenesis by proportional deoxyribonucleoside triphosphate accumulation in Escherichia coliLinda J Wheeler
Department of Biochemistry and Biophysics, Oregon State University, Corvallis, 97331-7305, USA
DNA Repair (Amst) 4:1450-6. 2005....
Characterization of SpPol4, a unique X-family DNA polymerase in Schizosaccharomyces pombeSergio González-Barrera
Centro de Biologia Molecular Severo Ochoa CSIC UAM, Universidad Autonoma, Madrid, Spain
Nucleic Acids Res 33:4762-74. 2005..Therefore, SpPol4 is a unique enzyme whose enzymatic properties are hybrid of those described for mammalian Polbeta, Pollambda and Polmu...
Motions of the fingers subdomain of klentaq1 are fast and not rate limiting: implications for the molecular basis of fidelity in DNA polymerasesPaul J Rothwell
Institute of Structural Molecular Biology, Birkbeck College and University College London, Malet Street, London WC1E 7HX, United Kingdom
Mol Cell 19:345-55. 2005..We propose that the rate-limiting step occurs after the closing of the fingers subdomain and is caused by local reorganization events in the active site...
Thermostable DNA polymerases can perform translesion synthesis using 8-oxoguanine and tetrahydrofuran-containing DNA templatesEkaterina A Belousova
Institute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, Lavrentieva Prospect 8, Novosibirsk 630090, Russia
Biochim Biophys Acta 1764:97-104. 2006..In all cases, DNA duplex containing THF as damage was processed to full length less effectively than DNA duplex containing 8-oxoguanine...
Mutagenic properties of 3-(deoxyguanosin-N2-yl)-2-acetylaminofluorene, a persistent acetylaminofluorene-derived DNA adduct in mammalian cellsManabu Yasui
Laboratory of Chemical Biology, Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, New York 11794-8651, USA
Biochemistry 43:15005-13. 2004....
A dideoxynucleotide-sensitive DNA polymerase activity characterized from endoreduplicating cells of mungbean (Vigna radiata L.) during ontogeny of cotyledonsSujit Roy
Department of Botany, Bose Institute, Kolkata, India
FEBS J 274:2005-23. 2007....
Increased dNTP binding affinity reveals a nonprocessive role for Escherichia coli beta clamp with DNA polymerase IVJeffrey G Bertram
Departments of Biological Sciences and Chemistry, Hedco Molecular Biology Laboratories, University of Southern California, University Park, Los Angeles, California 90089 1340, USA
J Biol Chem 279:33047-50. 2004..We show that the increased DNA polymerase IV-dNTP binding affinity is an intrinsic property of the DNA polymerase IV-beta clamp interaction and not an indirect consequence of an increased binding of DNA polymerase IV to DNA...
Molecular basis of selectivity of nucleoside triphosphate incorporation opposite O6-benzylguanine by sulfolobus solfataricus DNA polymerase Dpo4: steady-state and pre-steady-state kinetics and x-ray crystallography of correct and incorrect pairingRobert L Eoff
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
J Biol Chem 282:13573-84. 2007....
DNA sequencing by MALDI-TOF MS using alkali cleavage of RNA/DNA chimerasFlorence Mauger
Centre National de Genotypage, Bâtiment G2, 2 rue Gaston Cremieux, 91057 Evry Cedex, France
Nucleic Acids Res 35:e62. 2007..These differences between signatures are indicative of known, unidentified, rare and private mutations. This novel DNA sequencing protocol was applied to sequence the hypervariable region 1 (HV1) of mitochondrial DNA in 22 individuals...
A role for dNTP binding of human immunodeficiency virus type 1 reverse transcriptase in viral mutagenesisKellie K Weiss
Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 672, Rochester, New York 14642, USA
Biochemistry 43:4490-500. 2004..8- and 5.7-fold higher fidelities than wild-type viruses, respectively, indicating that the molecular interaction between HIV-1 RT and the dNTP substrate contributes to viral mutagenesis...
Molecular requirements for duplex recognition and cleavage by eukaryotic RNase III: discovery of an RNA-dependent DNA cleavage activity of yeast Rnt1pBruno Lamontagne
Groupe ARN/RNA Group, , , , Sherbrooke, Que, Canada J1H 5N4
J Mol Biol 338:401-18. 2004..The discovery of this novel RNA-dependent deoxyribonuclease activity has potential implications in devising new antiviral strategies that target actively transcribed DNA...
The properties of steric gate mutants reveal different constraints within the active sites of Y-family and A-family DNA polymerasesAngela M DeLucia
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA
J Biol Chem 281:27286-91. 2006..In Klenow fragment the templating base is more rigidly held, so that changes in base pair geometry would affect the dNTP position, allowing the Glu710 side chain to serve as a sensor of nascent mispairs...
Human DNA polymerase epsilon: enzymologic mechanism and gap-filling synthesisD J Mozzherin
Department of Pharmacological Sciences, University Medical Center, State University of New York at Stony Brook 11794 8651, USA
Biochemistry 35:3572-7. 1996..This observation is consistent with a specific role for pol epsilon in gap-filling in vivo. Gap-filling is essential for both replication and repair...
Fidelity of DNA polymerase epsilon holoenzyme from budding yeast Saccharomyces cerevisiaeKikuo Shimizu
The Department of Biochemistry and Molecular Biology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan
J Biol Chem 277:37422-9. 2002....
The mutational specificity of the Dbh lesion bypass polymerase and its implicationsOlga Potapova
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520-8114, USA
J Biol Chem 277:28157-66. 2002..We suspect that the unusual mutational specificity of Dbh (which is shared with other polymerases from the DinB branch of the bypass polymerase family) may be related to the type of DNA lesion(s) that it serves to bypass in vivo...
DNA sequence analysis with a modified bacteriophage T7 DNA polymerase. Effect of pyrophosphorolysis and metal ionsS Tabor
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115
J Biol Chem 265:8322-8. 1990....
Misincorporation and stalling at O(6)-methylguanine and O(6)-benzylguanine: evidence for inactive polymerase complexesAdrienne M Woodside
Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA
Biochemistry 41:1039-50. 2002..In summary, several lines of evidence indicate that the existence of a nonproductive polymerase complex best explains polymerase kinetics at DNA-carcinogen adducts, specifically O(6)-alkylguanine...
Effect of the O6 substituent on misincorporation kinetics catalyzed by DNA polymerases at O(6)-methylguanine and O(6)-benzylguanineAdrienne M Woodside
Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA
Biochemistry 41:1027-38. 2002..These results and others regarding polymerase stalling opposite O(6)-MeG and O(6)-BzG are discussed in the following paper in this issue [Woodside, A. M., and Guengerich, F. P. (2002) Biochemistry 41, 1039-1050]...
A DNA polymerase beta mutator mutant with reduced nucleotide discrimination and increased protein stabilityA M Shah
Department of Therapeutic Radiology and Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, USA
Biochemistry 40:11372-81. 2001..The structural changes of M282Lbeta ultimately lead to an overall reduction in polymerase fidelity...
Characterization of a DNA-cleaving deoxyribozymeN Carmi
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520-8103, USA
Bioorg Med Chem 9:2589-600. 2001..The structural, kinetic and mechanistic characteristics of this DNA-cleaving deoxyribozyme are reported...
Selection of deoxyribozyme ligases that catalyze the formation of an unnatural internucleotide linkageM Levy
Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, University of Texas at Austin, 78712, USA
Bioorg Med Chem 9:2581-7. 2001..The selected deoxyribozymes enhance the rate of ligation in part through the provision of a template that aligns the ligation junction and do not appear to require metal ions for catalysis...
Dynamics of DNA polymerase III holoenzyme of Escherichia coli in replication of a multiprimed templateA Kornberg
J Biol Chem 260:12875-83. 1985..Based on these findings, schemes can be considered for holoenzyme action at the replication fork of a duplex chromosome...
Significance of nucleobase shape complementarity and hydrogen bonding in the formation and stability of the closed polymerase-DNA complexL Dzantiev
Department of Chemistry, Wayne State University, Detroit, Michigan 48202, USA
Biochemistry 40:3215-21. 2001..Finally, a stable closed complex is not formed in the presence of a ddNTP or rNTP. These results are discussed in relation to the steric exclusion model for the nucleotide insertion...
Complexes of Rep protein with ATP and DNA as a basis for helicase actionN Arai
J Biol Chem 256:5287-93. 1981..These and related studies serve as guides to understanding the multiple interactions of rep protein with its ATP and DNA ligands that enable it to unwind duplex DNA at a replication fork...
Mechanism of primer-template-dependent conversion of dNTP leads to dNMP by T5 DNA polymeraseS K Das
J Biol Chem 255:7149-54. 1980..A simple probabilistic model of turnover is discussed...
A new RNA helicase isolated from HeLa cells that catalytically translocates in the 3' to 5' directionC G Lee
Graduate Program in Molecular Biology, Memorial Sloan Kettering Cancer Center, Sloan Kettering Institute, New York, New York 10021
J Biol Chem 267:4398-407. 1992..We propose that the enzyme can bind to both single-stranded RNA and DNA and hydrolyze ATP, but by virtue of its greater stability on RNA, the enzyme can only translocate on RNA possessing 3' single-stranded regions...
Single base extension (SBE) with proofreading polymerases and phosphorothioate primers: improved fidelity in single-substrate assaysDaniel Di Giusto
School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia
Nucleic Acids Res 31:e7. 2003..These results suggest that the use of PS primers and proofreading polymerases will offer a simple and cost-effective means to improve fidelity in a range of single-substrate SBE assay formats...
Complex restriction enzymes: NTP-driven molecular motorsAude A Bourniquel
Department of Molecular Microbiology, Biozentrum, University of Basel, Klingelbergstrasse 50 70, Switzerland
Biochimie 84:1047-59. 2002....
The effect of tautomeric constant on the specificity of nucleotide incorporation during DNA replication: support for the rare tautomer hypothesis of substitution mutagenesisVictoria H Harris
Centre for Chemical Biology, Department of Chemistry, Krebs Institute, University of Sheffield, Sheffield S3 7HF, UK
J Mol Biol 326:1389-401. 2003..Furthermore, they imply that DNA polymerases impose specific steric requirements on the base-pair during nucleotide incorporation...
Research Grants
- Targeting aberrant epigenetics by nanomedicineShujun Liu; Fiscal Year: 2010..4) targeted lipid-based nanocarrier delivery of chemo-compounds or oligo deoxyribonucleotides (ODNs) display more significant target downregulation thereby more pronounced anti-tumor activity in vitro ..
- Synthetic Models and Spectroscopy of Metal-Oxo ProteinsLawrence Que; Fiscal Year: 2006..a variety of functions in biology: dioxygen transport (hemerythrin), the conversion of ribonucleotides to deoxyribonucleotides (ribonucleotide reductase), iron storage (ferritin), phosphate ester hydrolysis (purple acid phosphatases), ..
- SYNTHETIC APPROACHES FOR MODELLING METAL-OXO PROTEINSLawrence Que; Fiscal Year: 1993..a variety of functions in biology-- dioxygen transport (hemerythrin), the conversion of ribonucleotides to deoxyribonucleotides (ribonucleotide reductase), phosphate ester hydrolysis (purple acid phosphatases), iron storage (ferritin), ..
- Electronic Structure and Reactions of Fe-oxo EnzymesLouis Noodleman; Fiscal Year: 2006..MMO) and ribonucleotide reductase (RNR), which hydroxylate alkanes and reduce ribonucleotides (NDP) to deoxyribonucleotides (dNDP), respectively...
- Electronic Structure and Reactions of Fe-oxo EnzymesLouis Noodleman; Fiscal Year: 2010..RNRs catalyze the transformation of ribonucleotides to deoxyribonucleotides, the first required and often rate limiting step in DNA synthesis...
- Electronic Structure and Reactions of Fe-oxo EnzymesLouis Noodleman; Fiscal Year: 2007..RNRs catalyze the transformation of ribonucleotides to deoxyribonucleotides, the first required and often rate limiting step in DNA synthesis...
- Regulation of ribonucleotide reductase in Aedes aegyptiDAPHNE PHAM; Fiscal Year: 2005DESCRIPTION (provided by the applicant): Ribonucleotide reductase (RNR) catalyzes the de novo synthesis of deoxyribonucleotides. Class I RNRs are alpha2Beta2 holoenzymes with homodimers denoted as Ri and R2...
- Iron Trafficking to Ribonucleotide ReductasesDANIEL KOSMAN; Fiscal Year: 2006..While not directly involved in the reduction of ribonucleotides to deoxyribonucleotides, this prosthetic group is essential to enzyme activity...
- ANTIHIV OLIGONUCLEOTIDES WITH REACTIVE FUNCTIONAL GROUPSPaul Miller; Fiscal Year: 2006..Chimeric anti-TAR and anti-RRE mr- OMPs that contain a tract of six deoxyribonucleotides flanked by four or five 2'-O-methylribonucleosides will be studied for their ability to form RNase H ..
- SYNTHETIC APPROACHES FOR MODELING METAL-OXO PROTEINSLawrence Que; Fiscal Year: 2002..a variety of functions in biology- -dioxygen transport (hemerythrin), the conversion of ribonucleotides to deoxyribonucleotides (ribonucleotide reductase), phosphate ester hydrolysis (purple acid phosphatases), and oxygen activation (..
- Oxygen Activation and Radical Transfer in Ribonucleotide Reductase from PathogensCarsten Krebs; Fiscal Year: 2010Ribonucleotide reductases (RNRs) provide deoxyribonucleotides for DNA synthesis and repair. The enzymes employ a conserved free-radical mechanism...
- Oxygen Activation and Radical Transfer in Ribonucleotide Reductase from PathogensCarsten Krebs; Fiscal Year: 2010Ribonucleotide reductases (RNRs) provide deoxyribonucleotides for DNA synthesis and repair. The enzymes employ a conserved free-radical mechanism...
- T CELL KINETICS AND SOURCES--EFFECTS OF HIV AND THERAPYMarc Hellerstein; Fiscal Year: 2002..infusion of [6,6-2H2] glucose, isolation of cells by fluorescence activated cell sorting and MS analysis of deoxyribonucleotides from DNA, as described previously. Comparisons include naive vs. memory. CD4+ vs. CD8+, thymic vs...
