deoxyribonucleotides

Summary

Summary: A purine or pyrimidine base bonded to a DEOXYRIBOSE containing a bond to a phosphate group.

Top Publications

  1. ncbi A suppressor of two essential checkpoint genes identifies a novel protein that negatively affects dNTP pools
    X 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
  2. pmc Abundant ribonucleotide incorporation into DNA by yeast replicative polymerases
    Stephanie A Nick McElhinny
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Proc Natl Acad Sci U S A 107:4949-54. 2010
  3. pmc Lack of sugar discrimination by human Pol mu requires a single glycine residue
    Jose 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
  4. pmc Highly mutagenic and severely imbalanced dNTP pools can escape detection by the S-phase checkpoint
    Dinesh Kumar
    Department of Medical Biochemistry and Biophysics, Umea University, SE 90187 Umea, Sweden
    Nucleic Acids Res 38:3975-83. 2010
  5. ncbi Regulation of mammalian ribonucleotide reduction and dNTP pools after DNA damage and in resting cells
    Pelle Håkansson
    Department of Medical Biochemistry and Biophysics, Umea University, SE 90187 Umea, Sweden
    J Biol Chem 281:7834-41. 2006
  6. pmc Quantitation of cellular deoxynucleoside triphosphates
    Paola Ferraro
    Department of Biology, University of Padova, 35131 Padova, Italy
    Nucleic Acids Res 38:e85. 2010
  7. pmc Thymidine kinase 2 (H126N) knockin mice show the essential role of balanced deoxynucleotide pools for mitochondrial DNA maintenance
    Hasan O Akman
    Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA
    Hum Mol Genet 17:2433-40. 2008
  8. ncbi DNA precursor metabolism and genomic stability
    Christopher K Mathews
    Department of Biochemistry and Biophysics, Oregon State University, 2011 Agricultural and Life Sciences Bldg, Corvallis, Oregon 97331 7305, USA
    FASEB J 20:1300-14. 2006
  9. ncbi Impaired function of p53R2 in Rrm2b-null mice causes severe renal failure through attenuation of dNTP pools
    Takashi 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
  10. ncbi Regulation by degradation, a cellular defense against deoxyribonucleotide pool imbalances
    Chiara Rampazzo
    Department of Biology, University of Padova, Via Ugo Bassi 58B, 35131 Padova, Italy
    Mutat Res 703:2-10. 2010

Research Grants

Detail Information

Publications204 found, 100 shown here

  1. ncbi A suppressor of two essential checkpoint genes identifies a novel protein that negatively affects dNTP pools
    X 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...
  2. pmc Abundant ribonucleotide incorporation into DNA by yeast replicative polymerases
    Stephanie A Nick McElhinny
    Laboratory of Molecular Genetics and Laboratory of Structural Biology, Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Proc Natl Acad Sci U S A 107:4949-54. 2010
    ....
  3. pmc Lack of sugar discrimination by human Pol mu requires a single glycine residue
    Jose 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...
  4. pmc Highly mutagenic and severely imbalanced dNTP pools can escape detection by the S-phase checkpoint
    Dinesh 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...
  5. ncbi Regulation of mammalian ribonucleotide reduction and dNTP pools after DNA damage and in resting cells
    Pelle Håkansson
    Department of Medical Biochemistry and Biophysics, Umea University, SE 90187 Umea, Sweden
    J Biol Chem 281:7834-41. 2006
    ....
  6. pmc Quantitation of cellular deoxynucleoside triphosphates
    Paola 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...
  7. pmc Thymidine kinase 2 (H126N) knockin mice show the essential role of balanced deoxynucleotide pools for mitochondrial DNA maintenance
    Hasan 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...
  8. ncbi DNA precursor metabolism and genomic stability
    Christopher K Mathews
    Department of Biochemistry and Biophysics, Oregon State University, 2011 Agricultural and Life Sciences Bldg, Corvallis, Oregon 97331 7305, USA
    FASEB J 20:1300-14. 2006
    ....
  9. ncbi Impaired function of p53R2 in Rrm2b-null mice causes severe renal failure through attenuation of dNTP pools
    Takashi 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)...
  10. ncbi Regulation by degradation, a cellular defense against deoxyribonucleotide pool imbalances
    Chiara 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...
  11. pmc Single-molecule microscopy reveals new insights into nucleotide selection by DNA polymerase I
    Radoslaw P Markiewicz
    Department of Chemistry, Wayne State University, Detroit, MI, USA
    Nucleic Acids Res 40:7975-84. 2012
    ..Our assay can also distinguish between primer binding to the polymerase or exonuclease domain and, contrary to ensemble-averaged studies, we find that stable exonuclease binding only occurs with a mismatched primer terminus...
  12. pmc Glutamine deprivation induces abortive s-phase rescued by deoxyribonucleotides in k-ras transformed fibroblasts
    Daniela Gaglio
    Department of Biotechnology and Biosciences, University of Milano Bicocca, Milan, Italy
    PLoS ONE 4:e4715. 2009
    ..Another metabolic adaptation of cancer cells, that has long been established, is their propensity to exhibit increased glutamine consumption, although the effects induced by glutamine deprivation on cancer cells are still controversial...
  13. ncbi Abasic DNA structure, reactivity, and recognition
    J 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)...
  14. ncbi Chemical primer extension at submillimolar concentration of deoxynucleotides
    Manuel Röthlingshöfer
    Institute for Organic Chemistry, University of Karlsruhe K I T, 76131 Karlsruhe, Germany
    J Org Chem 75:3945-52. 2010
    ..The method greatly simplifies chemical primer extension assays, further reduces the cost of such assays, and demonstrates the potential of the in situ activation approach...
  15. pmc Deoxyribonucleotide metabolism in cycling and resting human fibroblasts with a missense mutation in p53R2, a subunit of ribonucleotide reductase
    Giovanna Pontarin
    Department of Biology, University of Padova, Padova, Italy
    J Biol Chem 286:11132-40. 2011
    ..We speculate that this compensatory mechanism suffices to maintain mtDNA in fibroblasts but not in muscle cells with a larger content of mtDNA necessary for their high energy requirements...
  16. pmc Discrimination against purine-pyrimidine mispairs in the polymerase active site of DNA polymerase I: a structural explanation
    Dana T Minnick
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Proc Natl Acad Sci U S A 99:1194-9. 2002
    ..Moreover, this same side chain enhances the stability of incoming correct dNTPs, such that loss of this interaction on removal of the side chain leads to lower selectivity against mismatches involving incoming pyrimidines...
  17. pmc Mechanisms of mutagenesis in vivo due to imbalanced dNTP pools
    Dinesh Kumar
    Department of Medical Biochemistry and Biophysics, Umea University, SE 901 87 Umea, Sweden
    Nucleic Acids Res 39:1360-71. 2011
    ..An interesting mutational strand bias is observed in one rnr1 strain, suggesting that the S-phase checkpoint selectively prevents replication errors during leading strand replication...
  18. pmc Molecular architecture of a multifunctional MCM complex
    June Sanchez-Berrondo
    Structural Biology and Biocomputing Programme, Macromolecular Crystallography Group, Spanish National Cancer Research Center CNIO, c Melchor Fdez Almagro 3, 28029 Madrid, Spain
    Nucleic Acids Res 40:1366-80. 2012
    ....
  19. pmc Structural factors that determine selectivity of a high fidelity DNA polymerase for deoxy-, dideoxy-, and ribonucleotides
    Weina Wang
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 287:28215-26. 2012
    ..to discriminating against base pair mismatches, DNA polymerases exhibit a high degree of selectivity for deoxyribonucleotides over ribo- or dideoxynucleotides...
  20. ncbi A novel homozygous RRM2B missense mutation in association with severe mtDNA depletion
    Gittan 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.
  21. pmc Reverse transcriptases and genomic variability: the accuracy of DNA replication is enzyme specific and sequence dependent
    M Ricchetti
    Institut Pasteur, Unite de Physicochimie des Macromolecules Biologiques, URA1149 du CNRS, Paris, France
    EMBO J 9:1583-93. 1990
    ..Additional data, using a complementary DNA (positive) strand as a gag template support this hypothesis...
  22. pmc Discrimination between right and wrong purine dNTPs by DNA polymerase I from Bacillus stearothermophilus
    Michael Trostler
    Department of Chemistry and Biochemistry, University of Colorado, UCB 215, Boulder, Colorado 80309, USA
    Biochemistry 48:4633-41. 2009
    ....
  23. ncbi Is a thymine dimer replicated via a transient abasic site intermediate? A comparative study using non-natural nucleotides
    Babho 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...
  24. ncbi Deoxyribonucleotide pool imbalance stimulates deletions in HeLa cell mitochondrial DNA
    Shiwei 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...
  25. pmc The alternative aerobic ribonucleotide reductase of Escherichia coli, NrdEF, is a manganese-dependent enzyme that enables cell replication during periods of iron starvation
    Julia E Martin
    Department of Microbiology, University of Illinois, Urbana, IL 61801, USA
    Mol Microbiol 80:319-34. 2011
    ..Thus NrdEF supports DNA replication when iron is unavailable to activate the housekeeping NrdAB enzyme...
  26. ncbi The Schizosaccharomyces pombe replication inhibitor Spd1 regulates ribonucleotide reductase activity and dNTPs by binding to the large Cdc22 subunit
    Pelle Håkansson
    Department of Medical Biochemistry and Biophysics, Umea University, SE 901 87 Umea, Sweden
    J Biol Chem 281:1778-83. 2006
    ..This increase is smaller than the increase observed in budding yeast but of the same order as the dNTP pool increase when synchronous Schizosaccharomyces pombe cdc10 cells are going from G1 to S-phase...
  27. pmc An error-prone family Y DNA polymerase (DinB homolog from Sulfolobus solfataricus) uses a 'steric gate' residue for discrimination against ribonucleotides
    Angela 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...
  28. ncbi Allosteric regulation of Trypanosoma brucei ribonucleotide reductase studied in vitro and in vivo
    A Hofer
    Department of Medical Biochemistry and Biophysics, Umea University, S 901 87 Umea, Sweden
    J Biol Chem 273:34098-104. 1998
    ..This uncontrolled uptake of deoxyadenosine strongly inhibited trypanosome proliferation, a valuable observation in the search for new trypanocidal nucleoside analogues...
  29. pmc Macrophage tropism of HIV-1 depends on efficient cellular dNTP utilization by reverse transcriptase
    Tracy L Diamond
    Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Biol Chem 279:51545-53. 2004
    ....
  30. ncbi Evaluating the contribution of base stacking during translesion DNA replication
    Edmunds 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...
  31. ncbi The properties of steric gate mutants reveal different constraints within the active sites of Y-family and A-family DNA polymerases
    Angela 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...
  32. ncbi DNA sequence analysis with a modified bacteriophage T7 DNA polymerase. Effect of pyrophosphorolysis and metal ions
    S Tabor
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115
    J Biol Chem 265:8322-8. 1990
    ....
  33. ncbi Substrate specificity and phosphorylation of antiviral and anticancer nucleoside analogues by human deoxyribonucleoside kinases and ribonucleoside kinases
    An 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...
  34. ncbi Pre-steady-state kinetic studies of the fidelity of human DNA polymerase mu
    Michelle 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...
  35. pmc Bidentate and tridentate metal-ion coordination states within ternary complexes of RB69 DNA polymerase
    Shuangluo Xia
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520 8114, USA
    Protein Sci 21:447-51. 2012
    ..88 Å resolution. Our observations suggest that several distinct metal-ion coordination states can exist at the ground state in the polymerase active site and that base selectivity is unlikely to be based on metal-ion coordination alone...
  36. ncbi Significance of nucleobase shape complementarity and hydrogen bonding in the formation and stability of the closed polymerase-DNA complex
    L 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...
  37. pmc Mechanistic interplay among the M184I HIV-1 reverse transcriptase mutant, the central polypurine tract, cellular dNTP concentrations and drug sensitivity
    Sarah K Van Cor-Hosmer
    Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Virology 406:253-60. 2010
    ..These data support a mechanistic interaction between cPPT and M184I RT with respect to viral replication and sensitivity to 3TC...
  38. ncbi The mechanism of action of T7 DNA polymerase
    S DOUBLIE
    Department of Biological Chemistry and Molecular Pharmacology Harvard Medical School 240 Longwood Avenue Boston MA 02115 5730 USA
    Curr Opin Struct Biol 8:704-12. 1998
    ....
  39. ncbi The effect of tautomeric constant on the specificity of nucleotide incorporation during DNA replication: support for the rare tautomer hypothesis of substitution mutagenesis
    Victoria 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...
  40. ncbi Deoxynucleoside triphosphate and pyrophosphate binding sites in the catalytically competent ternary complex for the polymerase reaction catalyzed by DNA polymerase I (Klenow fragment)
    M Astatke
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520
    J Biol Chem 270:1945-54. 1995
    ..Mutations of Arg682, His734, and Tyr766 affect the binding of DNA, suggesting that these mutations, whose effect on dNTP binding is small, may influence dNTP binding indirectly via the positioning of the DNA template-primer...
  41. pmc Evidence for lesion bypass by yeast replicative DNA polymerases during DNA damage
    Nasim Sabouri
    Department of Medical Biochemistry and Biophysics, Umea University, SE 901 87 Umea, Sweden
    Nucleic Acids Res 36:5660-7. 2008
    The enzyme ribonucleotide reductase, responsible for the synthesis of deoxyribonucleotides (dNTP), is upregulated in response to DNA damage in all organisms...
  42. pmc Ribonucleotide reductase is not limiting for mitochondrial DNA copy number in mice
    Emil 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...
  43. ncbi Substrate specificity of vaccinia virus thymidylate kinase
    Dimitri Topalis
    Laboratoire d Enzymologie Moléculaire et Fonctionnelle, 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...
  44. ncbi Motions of the fingers subdomain of klentaq1 are fast and not rate limiting: implications for the molecular basis of fidelity in DNA polymerases
    Paul 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...
  45. ncbi 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...
  46. ncbi Dynamics of translesion DNA synthesis catalyzed by the bacteriophage T4 exonuclease-deficient DNA polymerase
    A J Berdis
    Department of Pharmacology, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA
    Biochemistry 40:7180-91. 2001
    ..Extension from the G:abasic or A:abasic site mispair generates significant elemental effects (between 5 and 20) and suggests that chemistry is at least partially rate-limiting for extension beyond either mispair...
  47. ncbi Mitochondria as determinant of nucleotide pools and chromosomal stability
    Claus Desler
    Department of Science, Systems and Models, Roskilde University, 4000 Roskilde, Denmark
    Mutat Res 625:112-24. 2007
    ..Our results suggest that mitochondria are central players in maintaining genomic stability and in controlling essential nuclear processes such as upholding a balanced supply of nucleotides...
  48. ncbi Oligo-2'-deoxyribonucleotides containing uracil modified at the 5-position with linkers ending with guanidinium groups
    Victoria Roig
    Centre de Biophysique Moleculaire, CNRS UPR 4301, rue Charles Sadron, 45071 Orleans Cedex 02, France
    J Am Chem Soc 125:4416-7. 2003
    We report here the synthesis and binding studies of oligo-2'-deoxyribonucleotides (ODNs) containing 2'-deoxyuridines, modified at the 5-position by linkers ending with either one or two guanidinium groups...
  49. pmc Fluorescence of 2-aminopurine reveals rapid conformational changes in the RB69 DNA polymerase-primer/template complexes upon binding and incorporation of matched deoxynucleoside triphosphates
    H Zhang
    Department of Molecular Biophysics and Biochemistry, Yale University, 333 Cedar Street, New Haven, CT 06520, USA
    Nucleic Acids Res 35:6052-62. 2007
    ....
  50. ncbi Evaluating the contributions of desolvation and base-stacking during translesion DNA synthesis
    Xuemei 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...
  51. ncbi Mitochondrial deoxyribonucleotide pools in deoxyguanosine kinase deficiency
    Ann 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...
  52. pmc Reduced dNTP binding affinity of 3TC-resistant M184I HIV-1 reverse transcriptase variants responsible for viral infection failure in macrophage
    Varuni K Jamburuthugoda
    Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
    J Biol Chem 283:9206-16. 2008
    ..This can restrict ground state dNTP binding and lead to inefficient DNA synthesis particularly at low dNTP concentrations, ultimately contributing to viral replication failure in macrophage and instability in vivo of the M184I mutation...
  53. pmc Human DNA polymerase iota utilizes different nucleotide incorporation mechanisms dependent upon the template base
    M 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
    ....
  54. ncbi A system for rapid DNA sequencing with fluorescent chain-terminating dideoxynucleotides
    J 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...
  55. ncbi Manganese substantially alters the dynamics of translesion DNA synthesis
    Heather 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...
  56. ncbi 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 inhibitors
    Z 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...
  57. ncbi The supply of exogenous deoxyribonucleotides accelerates the speed of the replication fork in early S-phase
    J Malinsky
    Department of Cell Biology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Albertov 4, 128 00 Prague 2, Czech Republic
    J Cell Sci 114:747-50. 2001
    ..In late S-phase, the administration of additional dNTPs has no effect on the speed of replication forks. The availability of 2'-deoxynucleotides seems to be a rate-limiting factor for DNA replication during early S-phase...
  58. ncbi Simultaneous determination of pyrimidine or purine deoxyribonucleoside triphosphates using a polymerase assay
    B 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...
  59. pmc Design and synthesis of a 3'-O-allyl photocleavable fluorescent nucleotide as a reversible terminator for DNA sequencing by synthesis
    Hameer Ruparel
    Columbia Genome Center, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 102:5932-7. 2005
    ....
  60. ncbi p53R2-dependent ribonucleotide reduction provides deoxyribonucleotides in quiescent human fibroblasts in the absence of induced DNA damage
    Giovanna Pontarin
    Department of Biology, University of Padova, I 35131 Padova, Italy
    J Biol Chem 282:16820-8. 2007
    ..Total ribonucleotide reduction in quiescent cells amounted to only 2-3% of cycling cells. We suggest that in quiescent cells an important function of p53R2 is to provide deoxynucleotides for mitochondrial DNA replication...
  61. ncbi Interference of gemcitabine triphosphate with the measurements of deoxynucleotides using an optimized DNA polymerase elongation assay
    K 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...
  62. ncbi A role for dNTP binding of human immunodeficiency virus type 1 reverse transcriptase in viral mutagenesis
    Kellie 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...
  63. pmc DNA precursor asymmetries in mammalian tissue mitochondria and possible contribution to mutagenesis through reduced replication fidelity
    Shiwei 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
    ....
  64. ncbi Variants of DNA polymerase Beta extend mispaired DNA due to increased affinity for nucleotide substrate
    Amit M Shah
    Yale University School of Medicine, Departments of Therapeutic Radiology and Genetics, New Haven, Connecticut 06520, USA
    Biochemistry 42:10709-17. 2003
    ....
  65. ncbi 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
    ....
  66. ncbi Defects in maintenance of mitochondrial DNA are associated with intramitochondrial nucleotide imbalances
    Neil 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...
  67. ncbi UvrA and UvrB enhance mutations induced by oxidized deoxyribonucleotides
    Mika Hori
    Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita ku, Sapporo 060 0812, Japan
    DNA Repair (Amst) 6:1786-93. 2007
    Oxidatively 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...
  68. ncbi Pre-steady-state kinetic studies of protein-template-directed nucleotide incorporation by the yeast Rev1 protein
    Craig 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...
  69. pmc Mismatched dNTP incorporation by DNA polymerase beta does not proceed via globally different conformational pathways
    Kuo Hsiang Tang
    Departments of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA
    Nucleic Acids Res 36:2948-57. 2008
    ....
  70. pmc Incorporation of reporter molecule-labeled nucleotides by DNA polymerases. II. High-density labeling of natural DNA
    Taurai 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...
  71. pmc Incorporation of reporter molecule-labeled nucleotides by DNA polymerases. I. Chemical synthesis of various reporter group-labeled 2'-deoxyribonucleoside-5'-triphosphates
    Gerald Giller
    Gnothis SA, PSE B, EPFL, CH 1015 Lausanne, Switzerland and Römerstrasse 7, 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...
  72. ncbi Maintaining precursor pools for mitochondrial DNA replication
    Christopher 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...
  73. ncbi Genetic and chemical rescue of the Saccharomyces cerevisiae phenotype induced by mitochondrial DNA polymerase mutations associated with progressive external ophthalmoplegia in humans
    Enrico 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...
  74. ncbi Deoxyribonucleotides and disorders of mitochondrial DNA integrity
    Ann 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...
  75. ncbi 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 beta
    Marina 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...
  76. pmc Enantioselectivity of human AMP, dTMP and UMP-CMP kinases
    Julie 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...
  77. pmc SNP genotyping using alkali cleavage of RNA/DNA chimeras and MALDI time-of-flight mass spectrometry
    Florence Mauger
    Centre National de Genotypage, Bâtiment G2 2 Rue Gaston Crémieux, 91057 Evry Cedex, France
    Nucleic Acids Res 34:e18. 2006
    ....
  78. pmc Structures of eukaryotic ribonucleotide reductase I provide insights into dNTP regulation
    Hai 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...
  79. pmc Mutagenic nucleotide incorporation and hindered translocation by a food carcinogen C8-dG adduct in Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4): modeling and dynamics studies
    Ling 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...
  80. ncbi Mitochondrial deoxyribonucleotides, pool sizes, synthesis, and regulation
    Chiara 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...
  81. ncbi Use of damaged DNA and dNTP substrates by the error-prone DNA polymerase X from African swine fever virus
    Sandeep 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...
  82. pmc Unbalanced deoxynucleotide pools cause mitochondrial DNA instability in thymidine phosphorylase-deficient mice
    Luis 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...
  83. ncbi Efficient bypass of a thymine-thymine dimer by yeast DNA polymerase, Poleta
    R 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...
  84. ncbi Determination of DNA structure in solution: enzymatic deuteration of the ribose 2' carbon
    Douglas 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...
  85. ncbi Terminal deoxynucleotidyl transferase indiscriminately incorporates ribonucleotides and deoxyribonucleotides
    J 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. 2001
    Terminal 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...
  86. ncbi Structural basis for allosteric substrate specificity regulation in anaerobic ribonucleotide reductases
    K 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...
  87. ncbi Crystal structures of human DNA polymerase beta complexed with DNA: implications for catalytic mechanism, processivity, and fidelity
    H 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...
  88. ncbi Guanine nucleosides and Jurkat cell death: roles of ATP depletion and accumulation of deoxyribonucleotides
    T 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...
  89. ncbi Fidelity of mutant HIV-1 reverse transcriptases: interaction with the single-stranded template influences the accuracy of DNA synthesis
    B Kim
    The Joseph Gottstein Memorial Cancer Research Laboratory, Department of Pathology, University of Washington, Seattle 98195 3577, USA
    Biochemistry 37:5831-9. 1998
    ....
  90. ncbi Efficient and accurate replication in the presence of 7,8-dihydro-8-oxoguanine by DNA polymerase eta
    L 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...
  91. pmc Erroneous incorporation of oxidized DNA precursors by Y-family DNA polymerases
    Masatomi 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...
  92. pmc Polymerase mu is a DNA-directed DNA/RNA polymerase
    Stephanie 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
    ....
  93. ncbi Crystal structures of the Klenow fragment of DNA polymerase I complexed with deoxynucleoside triphosphate and pyrophosphate
    L 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...
  94. ncbi Deoxyribonucleotides are maintained at normal levels in a yeast thioredoxin mutant defective in DNA synthesis
    E 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...
  95. pmc Transfer RNA aminoacylation: identification of a critical ribose 2'-hydroxyl-base interaction
    L 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...
  96. ncbi Inhibition of ribozymes by deoxyribonucleotides and the origin of DNA
    P 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...
  97. ncbi How E. coli DNA polymerase I (Klenow fragment) distinguishes between deoxy- and dideoxynucleotides
    M Astatke
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, 06520, USA
    J Mol Biol 278:147-65. 1998
    ....
  98. ncbi Abnormalities in uridine homeostatic regulation and pyrimidine nucleotide metabolism as a consequence of the deletion of the uridine phosphorylase gene
    Deliang 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...
  99. ncbi A DNA polymerase beta mutator mutant with reduced nucleotide discrimination and increased protein stability
    A 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...
  100. ncbi Characterization of a DNA-cleaving deoxyribozyme
    N 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...
  101. ncbi Selection of deoxyribozyme ligases that catalyze the formation of an unnatural internucleotide linkage
    M 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...

Research Grants62

  1. Targeting aberrant epigenetics by nanomedicine
    Shujun Liu; Fiscal Year: 2013
    ..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 ..
  2. Electronic Structure and Reactions of Fe-oxo Enzymes
    Louis Noodleman; Fiscal Year: 2010
    ..RNRs catalyze the transformation of ribonucleotides to deoxyribonucleotides, the first required and often rate limiting step in DNA synthesis...
  3. DEOXYRIBONUCLEOTIDE METABOLISM IN ESCHERICHIA COLI
    James Fuchs; Fiscal Year: 1992
    Ribonucleotide reductases catalyze the reduction of ribonucleotides to deoxyribonucleotides. The enzyme isolated from Escherichia coli has been extensively characterized and serves as the model for ribonucleotide reductases from other ..
  4. BIOLOGICAL METAL CLUSTERS--BIOPHYSICAL & MODEL STUDIES
    Michael Maroney; Fiscal Year: 1991
    ..diverse functions: oxygen transport, regulation of phosphate metabolism, conversion of ribonucleotides to deoxyribonucleotides ( a key step in DNA synthesis), and oxidation of methane to methanol...
  5. Ribonucleotide Reductase Inhibitors for Restenosis
    Howard Elford; Fiscal Year: 2009
    ..As such, we propose that the conversion of ribonucleotides to deoxyribonucleotides is an attractive therapeutic target to control cell proliferation and will reduce restenosis because it is ..
  6. Iron Trafficking to Ribonucleotide Reductases
    DANIEL KOSMAN; Fiscal Year: 2006
    ..While not directly involved in the reduction of ribonucleotides to deoxyribonucleotides, this prosthetic group is essential to enzyme activity...
  7. POTENTIAL NEW TOPICAL ANTI-PSORIASIS AGENTS
    Howard Elford; Fiscal Year: 1991
    ..The reduction of ribonucleotides to deoxyribonucleotides, catalyzed by ribonucleotide reductase, is a crucial and rate limiting step in the pathway leading to DNA ..
  8. IRON SITE OF RIBONUCLEOTIDE REDUCTASE
    Grant Bunker; Fiscal Year: 1992
    ..reductase (RR) catalyzes an essential step in the biosynthesis of DNA: the reduction of ribonucleotides to deoxyribonucleotides. Ribonucleotide reductase activity is essential for the survival of all cells...
  9. PURINE METABOLISM AND CHEMOTHERAPY IN GIARDIA LAMBLIA
    RANDOLPH BERENS; Fiscal Year: 1990
    ..This investigation will pursue these opportunities by determining if the organism can synthesize deoxyribonucleotides, it will characterize the enzyme which phoosphorylates these compounds, compare the structure- activity ..
  10. HISTONE HYPERACETYLATION IN REPLICATING SV40 CHROMOSOMES
    Barry Milavetz; Fiscal Year: 2009
    ..selected with antibodies which recognize proteins found only at the fork or labeled with biotin conjugated deoxyribonucleotides. In both strategies the status of histone hyperacetylation at various sites on the pre- and post-..
  11. T CELL KINETICS AND SOURCES--EFFECTS OF HIV AND THERAPY
    Marc 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...
  12. Is there a Class IV ribonucleotide reductase?
    Pamela Riggs Gelasco; Fiscal Year: 2003
    ..This so called Class I cofactor then participates in the conversion of ribonucleotides to deoxyribonucleotides, the rate limiting step in DNA synthesis...
  13. ANTIHIV OLIGONUCLEOTIDES WITH REACTIVE FUNCTIONAL GROUPS
    Paul 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 ..
  14. RIBONUCLEOTIDE REDUCTASE OF THE MALARIA PARASITE
    Debopam Chakrabarti; Fiscal Year: 2000
    ..Ribonucleotide reductase (RNR) catalyzes the rate-limiting step in the de novo synthesis of deoxyribonucleotides by the direct reduction of the corresponding ribonucleotides...
  15. INHIBITORS OF HUMAN RIBONUCLEOTIDE REDUCTASE
    RAYMOND BLAKLEY; Fiscal Year: 1980
    ..leichmannii, E. coli and other bacteria will be employed. The effect of natural 2'-deoxyribonucleotides and the analogs prepared as above will be tested as inhibitors of ribonucleotide reductase from a human ..
  16. RIBONUCLEOTIDE REDUCTASE AND CANCER CHEMOTHERAPY
    Howard Elford; Fiscal Year: 1980
    The conversion of ribonucleotides to deoxyribonucleotides is a critical step in the pathway leading to the formation of DNA. Our primary objective is the rational development of chemotherapeutic agents directed against this reaction...
  17. Ribonucleotide Reductase Antisense Strategy in AML
    Guido Marcucci; Fiscal Year: 2004
    ..RR is an enzyme operative in the synthetic pathway of deoxyribonucleotides and a potential key factor in induction of chemoresistance to ARA-C, a nucleoside analog incorporated in a ..
  18. INHIBITION OF RIBONUCLEOTIDE REDUCTASE IN GLIOMAS
    Wagner dos Santos; Fiscal Year: 2005
    ..Ribonucleotide reductase (RNR) is a key enzyme for converting ribonucleotides into deoxyribonucleotides, an activity crucial for DNA replication...
  19. Crosslinking Ribonucleotide Reductase Subunits to Study PCET Within
    Richard Kelley; Fiscal Year: 2009
    Ribonucleotide reductases (RNRs) are responsible for reducing ribonucleotides (NDPs) to deoxyribonucleotides (dNDPs) and are required in all organisms in order to make the monomeric precursors used in DNA replication and repair...
  20. De Novo Design of a Catalytically Active Di-Iron Carboxylate Enzyme
    AMANDA REIG; Fiscal Year: 2009
    ..of desaturated fatty acids, and the generation of a tyrosyl radical that facilitates the biosynthesis of deoxyribonucleotides. Their divergent reactivities, however, belie their structural similarities...
  21. TOPOLOGY AND MECHANISMS BY SITE-DIRECTED IMMUNOCHEMISTRY
    Jack Kyte; Fiscal Year: 2000
    ..Ribonucleotide reductase produces all of the deoxyribonucleotides needed for the duplication and repair of DNA in the cell.
  22. MECHANISM OF DMH-INDUCED CARCINOGENESIS
    JAE KANG; Fiscal Year: 1991
    ..calf thymus DNA and a number of selected enzyme proteins, as well as their primary constituents, namely, deoxyribonucleotides and amino acids...
  23. REGULATION OF DORMANCY IN M TUBERCULOSIS
    Harvey Rubin; Fiscal Year: 2003
    ..model of dormancy: These are: 1) the ribonucleotide reductase system that reduces ribonucleotides to deoxyribonucleotides--the rate limiting step in DNA synthesis, 2) the cytochrome bd oxidase system involved in growth under ..
  24. CONTROL OF DNA REPLICATION IN THE ANIMAL CELL CYCLE
    Michael Miller; Fiscal Year: 1980
    ..cultured mammalian cells to small and large molecules and have established conditions in which deoxyribonucleotides are incorporated into DNA at in vivo rates, resulting in replication of about 20% of the genome...
  25. SYNTHETIC AND BIOLOGICAL STUDIES OF NUCLEIC ACIDS
    H Khorana; Fiscal Year: 1980
    ..program can be categorized as follows: 1) Further development of the chemical methods for the synthesis of deoxyribonucleotides. 2) Structure-function relationships in the totally synthetic tyrosine tRNA gene. a...
  26. TRANSCRIPTIONAL REGULATION OF INSECT FERRITIN
    DAPHNE PHAM; Fiscal Year: 2002
    ....
  27. SSB PROTEINS AS ORGANIZERS OF DNA PRECURSOR BIOSYNTHESIS
    Christopher Mathews; Fiscal Year: 2001
    ..Characterization of the phosphorylation of SSB will explore the role of this modification on protein-protein and protein-DNA associations. ..
  28. Regulation of ribonucleotide reductase in Aedes aegypti
    DAPHNE PHAM; Fiscal Year: 2005
    DESCRIPTION (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...
  29. Chemistry to Improve Human Genomic Array Analysis Architectures
    Steven A Benner; Fiscal Year: 2010
    ..This proposal seeks funds to benchmark the improvements in array performance generated by these new technologies, improve them by a cycle of test and redesign, and provide them to the genomics community. ..
  30. DNA Sequencing using Nanopores
    Steven Benner; Fiscal Year: 2007
    ..These will then be targeted against specific sequences extracted from mammalian genomes. [unreadable] [unreadable]..
  31. Activating liver carcinogens in yeast by expressing CYP450 polymorphisms
    Michael Fasullo; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  32. CREATING MUTANT ENZYMES FOR GENE THERAPY OF CANCER
    LAWRENCE LOEB; Fiscal Year: 2007
    ..abstract_text> ..
  33. Semi-artificial nanomachines for detection of DNA damage and apoptosis
    VLADIMIR DIDENKO; Fiscal Year: 2008
    ..abstract_text> ..
  34. Polymerases for Sequencing by Synthesis
    Steven Benner; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  35. Role of p170 in lung tumorigenesis
    Jian Ting Zhang; Fiscal Year: 2007
    ..This work will certainly add to our understanding of the functional mechanism of translation initiation of protein synthesis. ..
  36. Mechanism of Redox Regulation by Ape1/Ref-1
    Millie M Georgiadis; Fiscal Year: 2010
    ..We propose here to elucidate the mechanism of the redox function of Ape1 and explore its role in tumor cell response following treatment with DNA damaging agents. ..
  37. The Werner Syndrome Protein in DNA Replication, Mutagenesis and Genomic Stability
    Lawrence A Loeb; Fiscal Year: 2010
    ..All of the procedures have been established and are ongoing in our laboratory and can be completed within two years. ..
  38. Targeting the oligomerization of human ABCG2
    Jian Ting Zhang; Fiscal Year: 2009
    ..This work may also lead us to the discovery of a new class of therapeutic agents that can help overcome drug-resistant cancers. ..
  39. Studies of redox-active sites in Photosystem II
    Victor S Batista; Fiscal Year: 2010
    ..abstract_text> ..
  40. Homeostatic Regulation of Folate Metabolism
    Patrick J Stover; Fiscal Year: 2010
    ..5. regulation of cSHMT by folate/choline preserves dTMP pools at the expense of AdoMet synthesis. The long-term goals of this project are: 1. to define homeostatic mechanisms used bv cells to regulate folate metabolism. ..
  41. REGULATION OF FOLATE CATABOLISM
    PATRICK STOVER; Fiscal Year: 2007
    ..2). to determine the risk that folate catabolism contributes to folate-associated pathologies. (3). to establish relationships between catecholamines and folate metabolism. ..
  42. EVOLUTION OF THE RIBONUCLEASE SUPERFAMILY
    Steven Benner; Fiscal Year: 2001
    ....
  43. MECHANISM OF DRUG BINDING TO P-GLYCOPROTEIN
    Jian Ting Zhang; Fiscal Year: 2001
    ..This work may lead us to the discovery of a new family of chaperone proteins associated with ribosomes that are important in determining the folding of membrane proteins co-translationally. ..
  44. DNA REPAIR AND CANCER PRONE HEREDITARY HUMAN DISEASE
    Errol Friedberg; Fiscal Year: 2002
    ....
  45. LETHAL MUTAGENESIS OF HIV BY DEOXYNUCLEOSIDE ANALOGS
    LAWRENCE LOEB; Fiscal Year: 2002
    ....
  46. Novel Targets for Treatment of Smallpox
    Stewart Shuman; Fiscal Year: 2003
    ....
  47. VACCINIA VIRUS DNA TOPOISOMERASE
    Stewart Shuman; Fiscal Year: 2006
    ..5) Biochemical and genetic characterization of the TopIB proteins from Mycobacterium avium, Mycobacterium smegmatis, and Pseudomonas aeurginosa. ..
  48. Free radicals detection in aging brain by fullerenes
    VLADIMIR DIDENKO; Fiscal Year: 2003
    ..At a later stage free radicals will be monitored using magnetic resonance tracer and MRI detection. ..
  49. RADIATION INDUCTION OF GENOMIC REARRANGEMENTS IN YEAST
    Michael Fasullo; Fiscal Year: 2004
    ..abstract_text> ..
  50. Targeted Assisted Combinational Synthesis
    Steven Benner; Fiscal Year: 2004
    ..abstract_text> ..
  51. FASEB Summer Conference: Folate, B12 and 1C Metabolism
    PATRICK STOVER; Fiscal Year: 2004
    ..Similarly, the poster sessions also highlight the activities and needs of the younger participants. ..
  52. DNA REPAIR AND ITS RELATIONSHIP TO CARCINOGENESIS
    Errol Friedberg; Fiscal Year: 2001
    ..There is reason to believe that the proteins encoded by these genes operate in a different chromatin-modulating complex, and it is proposed to isolate and characterize this putative complex as well. ..
  53. Recognition of Multiply Damaged Sites in DNA
    Carlos de Los Santos; Fiscal Year: 2005
    ..Additionally, it would afford additional time to the applicant for the establishment of an independent research program in his laboratory. ..
  54. NON-STANDARD BASE PAIRS AS BIOMEDICAL RESEARCH TOOLS
    Steven Benner; Fiscal Year: 2004
    ....
  55. Structural studies of protein-nucleic acid interactions
    Millie Georgiadis; Fiscal Year: 2005
    ..These studies provide a unique opportunity to compare biologically relevant nucleic acid interactions of the CTh with different proteins. ..
  56. Herpes virus infection in human glial precursors
    David Mock; Fiscal Year: 2005
    ..Potential confounding "direct" effects of the virus will be eliminated through the use of 0.1 ? pore-size membranes in a transwell format which effectively excludes infectious virus. ..
  57. DEVELOPMENT OF AN ORAL DRUG FOR SMALLPOX TREATMENT
    George Painter; Fiscal Year: 2007
    ..Upon FDA approval, a Phase I trial will be initiated to evaluate the safety, tolerability and pharmacokinetics of a single, escalating dose in human volunteers. ..
  58. Environmental Mutagen Society, 34th Annual Meeting
    LAWRENCE LOEB; Fiscal Year: 2003
    ..Awards will be made to US speakers whose major area of interest is in carcinogenesis. ..
  59. MOLECULAR BASES OF MULTIDRUG RESISTANCE IN CANCERS
    Jian Ting Zhang; Fiscal Year: 2001
    ..Additionally, this study will increase our understanding of how specific protein topological structures are related to transport functions in general. ..
  60. MOUSE MODELS OF DNA REPAIR - DEFECTIVE HUMAN DISEASES
    Errol Friedberg; Fiscal Year: 2011
    ..abstract_text> ..
  61. A Genome Sequence Survey of Enterocytozoon bieneusi
    Donna Akiyoshi; Fiscal Year: 2006
    ..c. Establishment of a website to provide access to the sequence data and clones by the scientific community. ..