dna directed dna polymerase

Summary

Summary: DNA-dependent DNA polymerases found in bacteria, animal and plant cells. During the replication process, these enzymes catalyze the addition of deoxyribonucleotide residues to the end of a DNA strand in the presence of DNA as template-primer. They also possess exonuclease activity and therefore function in DNA repair. EC 2.7.7.7.

Top Publications

  1. ncbi Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging
    G C Kujoth
    Departments of Genetics and Medical Genetics, University of Wisconsin, Madison, WI 53706, USA
    Science 309:481-4. 2005
  2. pmc Mutations in the ubiquitin binding UBZ motif of DNA polymerase eta do not impair its function in translesion synthesis during replication
    Narottam Acharya
    Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, 6 104 Blocker Medical Research Building, 301 University Blvd, Galveston, TX 77555 1061, USA
    Mol Cell Biol 27:7266-72. 2007
  3. ncbi Premature ageing in mice expressing defective mitochondrial DNA polymerase
    Aleksandra Trifunovic
    Department of Medical Nutrition, Karolinska Institutet, Novum, Karolinska University Hospital, S 141 86 Stockholm, Sweden
    Nature 429:417-23. 2004
  4. ncbi PCNA, the maestro of the replication fork
    George Lucian Moldovan
    Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18 82152 Martinsried, Germany
    Cell 129:665-79. 2007
  5. ncbi The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta
    C Masutani
    Institute for Molecular and Cellular Biology, Osaka University, Suita, Japan
    Nature 399:700-4. 1999
  6. pmc Rapid amplification of plasmid and phage DNA using Phi 29 DNA polymerase and multiply-primed rolling circle amplification
    F B Dean
    Molecular Staging, Inc, New Haven, Connecticut 06511, USA
    Genome Res 11:1095-9. 2001
  7. pmc Eukaryotic translesion polymerases and their roles and regulation in DNA damage tolerance
    Lauren S Waters
    Department of Biology, Massachusetts Institute of Technology, Building 68, Room 653, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Microbiol Mol Biol Rev 73:134-54. 2009
  8. ncbi Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis
    Marzena Bienko
    Institute for Biochemistry II, Goethe University Medical School, Theodor Stern Kai 7, 60590 Frankfurt, Germany
    Science 310:1821-4. 2005
  9. ncbi The Y-family of DNA polymerases
    H Ohmori
    Mol Cell 8:7-8. 2001
  10. pmc A new yeast poly(A) polymerase complex involved in RNA quality control
    Stepanka Vanacova
    Department of Cell Biology, Biozentrum, University of Basel, Basel, Switzerland
    PLoS Biol 3:e189. 2005

Research Grants

  1. The XP Variant: A Human Mutator Gene for UV Damage
    James Cleaver; Fiscal Year: 2005
  2. MOUSE MODELS OF DNA REPAIR - DEFECTIVE HUMAN DISEASES
    Errol Friedberg; Fiscal Year: 2011
  3. DNA Damage and Neurodegeneration in Cockayne Syndrome
    James Cleaver; Fiscal Year: 2009
  4. DNA-PROTEIN COMPLEX OF BACILLUS SUBTILITS PHAGE 029
    Margarita Salas; Fiscal Year: 2003
  5. DNA REPAIR AND ITS RELATIONSHIP TO CARCINOGENESIS
    Errol Friedberg; Fiscal Year: 2001
  6. DNA REPAIR AND CANCER PRONE HEREDITARY HUMAN DISEASE
    Errol Friedberg; Fiscal Year: 2002
  7. KINETIC ANALYSIS OF MICROTUBULE-DEPENDENT ATPASES
    Kenneth Johnson; Fiscal Year: 2003
  8. RE-ENGINEERING THE DIAMETER OF THE DOULBE HELIX
    Eric T Kool; Fiscal Year: 2010
  9. CHEMICAL AND BIOLOGICAL MIMICRY OF TELOMERASE
    ERIC KOOL; Fiscal Year: 2007
  10. Elementary Steps in DNA Polymerization
    Kenneth Johnson; Fiscal Year: 2008

Detail Information

Publications280 found, 100 shown here

  1. ncbi Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging
    G C Kujoth
    Departments of Genetics and Medical Genetics, University of Wisconsin, Madison, WI 53706, USA
    Science 309:481-4. 2005
    ..The levels of apoptotic markers were also found to increase during aging in normal mice. Thus, accumulation of mtDNA mutations that promote apoptosis may be a central mechanism driving mammalian aging...
  2. pmc Mutations in the ubiquitin binding UBZ motif of DNA polymerase eta do not impair its function in translesion synthesis during replication
    Narottam Acharya
    Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, 6 104 Blocker Medical Research Building, 301 University Blvd, Galveston, TX 77555 1061, USA
    Mol Cell Biol 27:7266-72. 2007
    ..These observations lead us to suggest that the binding of Ub on PCNA via its UBZ domain is not a necessary requirement for the ability of polymerase eta to function in TLS during replication...
  3. ncbi Premature ageing in mice expressing defective mitochondrial DNA polymerase
    Aleksandra Trifunovic
    Department of Medical Nutrition, Karolinska Institutet, Novum, Karolinska University Hospital, S 141 86 Stockholm, Sweden
    Nature 429:417-23. 2004
    ..Our results thus provide a causative link between mtDNA mutations and ageing phenotypes in mammals...
  4. ncbi PCNA, the maestro of the replication fork
    George Lucian Moldovan
    Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18 82152 Martinsried, Germany
    Cell 129:665-79. 2007
    ..Switching of PCNA partners may be triggered by affinity-driven competition, phosphorylation, proteolysis, and modification of PCNA by ubiquitin and SUMO...
  5. ncbi The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta
    C Masutani
    Institute for Molecular and Cellular Biology, Osaka University, Suita, Japan
    Nature 399:700-4. 1999
    ..Together, these results indicate that DNA polymerase eta could be the XPV gene product...
  6. pmc Rapid amplification of plasmid and phage DNA using Phi 29 DNA polymerase and multiply-primed rolling circle amplification
    F B Dean
    Molecular Staging, Inc, New Haven, Connecticut 06511, USA
    Genome Res 11:1095-9. 2001
    ..Amplified products can also be used for in vitro cloning, library construction, and other molecular biology applications...
  7. pmc Eukaryotic translesion polymerases and their roles and regulation in DNA damage tolerance
    Lauren S Waters
    Department of Biology, Massachusetts Institute of Technology, Building 68, Room 653, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Microbiol Mol Biol Rev 73:134-54. 2009
    ..Given the role of these translesion polymerases in mutagenesis, we discuss the significant regulatory mechanisms that control the five known eukaryotic translesion polymerases: Rev1, Pol zeta, Pol kappa, Pol eta, and Pol iota...
  8. ncbi Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis
    Marzena Bienko
    Institute for Biochemistry II, Goethe University Medical School, Theodor Stern Kai 7, 60590 Frankfurt, Germany
    Science 310:1821-4. 2005
    ..Our results indicate that Ub-binding domains of Y-family polymerases play crucial regulatory roles in TLS...
  9. ncbi The Y-family of DNA polymerases
    H Ohmori
    Mol Cell 8:7-8. 2001
  10. pmc A new yeast poly(A) polymerase complex involved in RNA quality control
    Stepanka Vanacova
    Department of Cell Biology, Biozentrum, University of Basel, Basel, Switzerland
    PLoS Biol 3:e189. 2005
    ..This polyadenylation-mediated RNA surveillance resembles the role of polyadenylation in bacterial RNA turnover...
  11. ncbi 8-oxo-guanine bypass by human DNA polymerases in the presence of auxiliary proteins
    Giovanni Maga
    Institute of Molecular Genetics IGM CNR, via Abbiategrasso 207, I 27100 Pavia, Italy
    Nature 447:606-8. 2007
    ....
  12. ncbi Crystal structure of a bacteriophage T7 DNA replication complex at 2.2 A resolution
    S DOUBLIE
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 391:251-8. 1998
    ..The structure illustrates how nucleotides are selected in a template-directed manner, and provides a structural basis for a metal-assisted mechanism of phosphoryl transfer by a large group of related polymerases...
  13. pmc Overexpression of human DNA polymerase mu (Pol mu) in a Burkitt's lymphoma cell line affects the somatic hypermutation rate
    Jose F Ruiz
    Centro de Biologia Molecular Severo Ochoa CSIC UAM, Universidad Autonoma, Madrid, Spain
    Nucleic Acids Res 32:5861-73. 2004
    ....
  14. 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...
  15. 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
    ....
  16. 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...
  17. pmc DNA polymerase mu (Pol mu), homologous to TdT, could act as a DNA mutator in eukaryotic cells
    O Dominguez
    Centro de Biologia Molecular Severo Ochoa CSIC UAM, Centro Nacional de Biotecnologia CSIC, Universidad Autonoma, 28049 Madrid, Spain
    EMBO J 19:1731-42. 2000
    ..Therefore, Pol mu is a good candidate to be the mutator polymerase responsible for somatic hyper- mutation of immunoglobulin genes...
  18. ncbi Mycobacterial Ku and ligase proteins constitute a two-component NHEJ repair machine
    Marina Della
    Cambridge Institute for Medical Research, University of Cambridge, Department of Haematology, Hills Road, Cambridge CB2 2XY, UK
    Science 306:683-5. 2004
    ..These results demonstrate that prokaryotic Ku and ligase form a bona fide NHEJ system that encodes all the recognition, processing, and ligation activities required for DSB repair...
  19. pmc The DNA polymerase gamma Y955C disease variant associated with PEO and parkinsonism mediates the incorporation and translesion synthesis opposite 7,8-dihydro-8-oxo-2'-deoxyguanosine
    Maria A Graziewicz
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Hum Mol Genet 16:2729-39. 2007
    ....
  20. ncbi Interaction of human DNA polymerase eta with monoubiquitinated PCNA: a possible mechanism for the polymerase switch in response to DNA damage
    Patricia L Kannouche
    Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RQ, United Kingdom
    Mol Cell 14:491-500. 2004
    ..Our findings provide an attractive mechanism by which monoubiquitination of PCNA might mediate the polymerase switch...
  21. pmc A novel strategy to engineer DNA polymerases for enhanced processivity and improved performance in vitro
    Yan Wang
    Department of Research and Development, MJ Bioworks Inc, 7000 Shoreline Court, South San Francisco, CA 94080, USA
    Nucleic Acids Res 32:1197-207. 2004
    ..This technology has the potential to broadly improve the performance of nucleic acid modifying enzymes...
  22. ncbi DNA joint dependence of pol X family polymerase action in nonhomologous end joining
    James M Daley
    Graduate Program in Cellular and Molecular Biology and Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109 0602, USA
    J Biol Chem 280:29030-7. 2005
    ..Finally, mammalian Pol X polymerases were able to differentially complement a pol4 mutation depending on the joint structure, demonstrating that these polymerases can participate in yeast NHEJ but with distinct properties...
  23. pmc A role for REV3 in mutagenesis during double-strand break repair in Saccharomyces cerevisiae
    S L Holbeck
    National Cancer Institute Frederick Cancer Research and Development Center, ABL Basic Research Program, Maryland 21702 1201, USA
    Genetics 147:1017-24. 1997
    ..Analysis of spontaneous reversion in haploid strains suggested that Rev3p had a greater role in making point mutations than in frameshift mutations...
  24. ncbi Immunoglobulin kappa light chain gene rearrangement is impaired in mice deficient for DNA polymerase mu
    Barbara Bertocci
    Institut National Français de Recherche Médicale U373, Faculte de Medecine Necker Enfants Malades, 156 rue de Vaugirard, 75730 Paris 15, France
    Immunity 19:203-11. 2003
    ..Pol mu appears, therefore, as a key element contributing to the relative homogeneity in size of light chain CDR3 and taking part in Ig gene rearrangement at a stage where TdT is no longer expressed...
  25. ncbi Evidence that in xeroderma pigmentosum variant cells, which lack DNA polymerase eta, DNA polymerase iota causes the very high frequency and unique spectrum of UV-induced mutations
    Yun Wang
    Carcinogenesis Laboratory, Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan, USA
    Cancer Res 67:3018-26. 2007
    ..These data strongly support the hypothesis that in cells lacking Pol eta, Pol iota is responsible for the high frequency and abnormal spectrum of UV-induced mutations, and ultimately their malignant transformation...
  26. pmc Localization of DNA polymerases eta and iota to the replication machinery is tightly co-ordinated in human cells
    Patricia Kannouche
    Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RQ, Cancer Research UK London Research Institute, 44, Lincoln s Inn Fields, London WC2A 3PX, UK
    EMBO J 21:6246-56. 2002
    ..Our results provide strong evidence that poleta targets poliota to the replication machinery, where it may play a general role in maintaining genome integrity as well as participating in translesion DNA synthesis...
  27. pmc Surveillance of nuclear-restricted pre-ribosomes within a subnucleolar region of Saccharomyces cerevisiae
    Christophe Dez
    Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK
    EMBO J 25:1534-46. 2006
    ..Localization of pre-ribosomes to this focus was lost in sda1-2 strains lacking Trf4p or Rrp6p. We designate this nucleolar focus the No-body and propose that it represents a site of pre-ribosome surveillance...
  28. pmc Dissecting mechanisms of nuclear mRNA surveillance in THO/sub2 complex mutants
    Mathieu Rougemaille
    Centre National de la Recherche Scientifique, Centre de Genetique Moleculaire, Gif sur Yvette, France
    EMBO J 26:2317-26. 2007
    ....
  29. ncbi Human DNA polymerase kappa encircles DNA: implications for mismatch extension and lesion bypass
    Samer Lone
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, Box 1677, 1425 Madison Avenue, New York, NY 10029, USA
    Mol Cell 25:601-14. 2007
    ....
  30. ncbi Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions
    G Van Goethem
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, Born Bunge Foundation, University of Antwerp, Universiteitsplein 1 B 2610 Antwerpen, Belgium
    Nat Genet 28:211-2. 2001
    ..We identified three additional POLG missense mutations compatible with recessive PEO In two nuclear families. POLG is the only DNA polymerase responsible for mtDNA replication...
  31. pmc Controlling the subcellular localization of DNA polymerases iota and eta via interactions with ubiquitin
    Brian S Plosky
    Laboratory of Genomic Integrity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 2725, USA
    EMBO J 25:2847-55. 2006
    ....
  32. pmc Ubiquitinated proliferating cell nuclear antigen activates translesion DNA polymerases eta and REV1
    Parie Garg
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, 660 South Euclid, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 102:18361-6. 2005
    ..We propose that ubiquitination of PCNA increases its functionality as a sliding clamp to promote mutagenic DNA replication...
  33. pmc Polkappa protects mammalian cells against the lethal and mutagenic effects of benzo[a]pyrene
    Tomoo Ogi
    Laboratories of Gene Information Analysis and Signal Transduction, Institute for Virus Research, Kyoto University, Shogoin Kawara cho 53, Sakyo ku, Japan
    Proc Natl Acad Sci U S A 99:15548-53. 2002
    ..Thus, our results indicate that Polkappa plays an important role in suppressing mutations at DNA lesions generated by B[a]P...
  34. ncbi hRAD30 mutations in the variant form of xeroderma pigmentosum
    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 285:263-5. 1999
    ..These results indicate that defects in hRAD30 cause XP-V, and they suggest that error-free replication of UV lesions by hRad30 plays an important role in minimizing the incidence of sunlight-induced skin cancers...
  35. pmc Mitochondrial DNA polymerase W748S mutation: a common cause of autosomal recessive ataxia with ancient European origin
    Anna H Hakonen
    Research Program of Neurosciences, Biomedicum Helsinki, Helsinki, Finland
    Am J Hum Genet 77:430-41. 2005
    ....
  36. pmc Rad18 guides poleta to replication stalling sites through physical interaction and PCNA monoubiquitination
    Kenji Watanabe
    Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan
    EMBO J 23:3886-96. 2004
    ..These results suggest that Rad18 is crucial for recruitment of poleta to the damaged site through protein-protein interaction and PCNA monoubiquitination...
  37. ncbi Nonoverlapping functions of DNA polymerases mu, lambda, and terminal deoxynucleotidyltransferase during immunoglobulin V(D)J recombination in vivo
    Barbara Bertocci
    INSERM U783, Faculté de Médecine René Descartes, Site Necker Enfants Malades, 156 rue de Vaugirard, 75730 Paris Cedex 15, France
    Immunity 25:31-41. 2006
    ....
  38. ncbi Break-induced replication and telomerase-independent telomere maintenance require Pol32
    John R Lydeard
    MS029 Rosenstiel Centre, Brandeis University, Waltham, Massachusetts 02454 9110, USA
    Nature 448:820-3. 2007
    ..We also note that Pol32 homologues have been identified both in fission yeast and in metazoans where telomerase-independent survivors with alternative telomere maintenance have also been identified...
  39. pmc Cell-free cloning using phi29 DNA polymerase
    Clyde A Hutchison
    Synthetic Biology Group, The J Craig Venter Institute, Rockville, MD 20850, USA
    Proc Natl Acad Sci U S A 102:17332-6. 2005
    ..These include environmental DNA samples that have proven difficult to clone and synthetic genes encoding toxic products. The method may also speed genome sequencing by eliminating the need for biological cloning...
  40. ncbi Phenotypic spectrum associated with mutations of the mitochondrial polymerase gamma gene
    Rita Horvath
    Metabolic Diseases Centre, Munich Schwabing, Institutes of Clinical Chemistry, Molecular Diagnostics and Mitochondrial Genetics, Academic Hospital Schwabing Munich, Germany
    Brain 129:1674-84. 2006
    ..1399G-->A (A467T) is common in children, but complete POLG1 sequencing is required to identify multiple mutations that can have complex implications for genetic counselling...
  41. ncbi The overexpression of specialized DNA polymerases in cancer
    Mark R Albertella
    KuDOS Pharmaceuticals Limited, 327 Cambridge Science Park, Milton Road, Cambridge CB4 OWG, UK
    DNA Repair (Amst) 4:583-93. 2005
    ..These observations suggest that specialised DNA polymerases, and particularly pol beta, could be considered both as caretaker genes altered during tumorigenesis, and as potential drug targets to sensitise tumors to chemotherapy...
  42. ncbi A coproofreading Zn(2+)-dependent exonuclease within a bacterial replicase
    Natalie M Stano
    Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
    Nat Struct Mol Biol 13:458-9. 2006
    ..Here we demonstrate that the alpha php domain contains a novel Zn(2+)-dependent 3' --> 5' exonuclease that preferentially removes mispaired nucleotides, providing the first example of a coediting nuclease...
  43. ncbi Cellular DNA replicases: components and dynamics at the replication fork
    Aaron Johnson
    Howard Hughes Medical Institute, New York City, New York 10021 6399, USA
    Annu Rev Biochem 74:283-315. 2005
    ..Twin polymerases and clamps coordinate their actions with a clamp loader and yet other proteins to form a replisome machine that advances the replication fork...
  44. pmc The roles of REV3 and RAD57 in double-strand-break-repair-induced mutagenesis of Saccharomyces cerevisiae
    Alison J Rattray
    Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA
    Genetics 162:1063-77. 2002
    ..We also find that REV3 is required for the repair of MMS-induced lesions when recombinational repair is compromised. Our data suggest that Rad55p/Rad57p help limit the generation of substrates that require pol zeta during recombination...
  45. pmc Rad18 regulates DNA polymerase kappa and is required for recovery from S-phase checkpoint-mediated arrest
    Xiaohui Bi
    Department of Genetics and Genomics, Boston University School of Medicine, 80 E Concord St, Boston, MA 02118, USA
    Mol Cell Biol 26:3527-40. 2006
    ..Recruitment of Polkappa to ubiquitinated PCNA enables lesion bypass and eliminates stalled forks, thereby attenuating the S-phase checkpoint...
  46. ncbi Antisense RNA stabilization induces transcriptional gene silencing via histone deacetylation in S. cerevisiae
    Jurgi Camblong
    Department of Cell Biology, Sciences III, University of Geneva, 30 quai E Ansermet, 1211 Geneva 4, Switzerland
    Cell 131:706-17. 2007
    ....
  47. pmc Characterization of the 3' exonuclease subunit DP1 of Methanococcus jannaschii replicative DNA polymerase D
    Maarit Jokela
    Biocenter Oulu and Department of Biochemistry, PO Box 3000, FIN 90014 University of Oulu, Finland
    Nucleic Acids Res 32:2430-40. 2004
    ..MjaDP1 acts as a unidirectional, non-processive exonuclease preferring mispaired nucleotides and single-stranded DNA, suggesting that MjaDP1 functions as the proofreading exonuclease of archaeal family D DNA polymerase...
  48. pmc Enhancement of DNA, cDNA synthesis and fidelity at high temperatures by a dimeric single-stranded DNA-binding protein
    Celia Perales
    Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas Universidad Autonoma de Madrid, Campus de Cantoblanco, 28049 Madrid, Spain
    Nucleic Acids Res 31:6473-80. 2003
    ..thermophilus. TthSSB was also able to bind single-stranded RNA, allowing a dramatic enhancement of the reverse transcription activity of its cognate Tth DNA polymerase during cDNA synthesis...
  49. pmc In vivo consequences of putative active site mutations in yeast DNA polymerases alpha, epsilon, delta, and zeta
    Y I Pavlov
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    Genetics 159:47-64. 2001
    ..This is supported by the observation that the pol3-Y708A mutation is recessive and its mutator effect is partially suppressed by disruption of the REV3 gene...
  50. ncbi Recognition of deaminated bases by archaeal family-B DNA polymerases
    Bernard A Connolly
    Institute for Cell and Molecular Biosciences ICaMB, University of Newcastle, Newcastle upon Tyne NE2 4HH, UK
    Biochem Soc Trans 37:65-8. 2009
    ..The possible role of read-ahead recognition of uracil/hypoxanthine in DNA repair is discussed, as is the observation that the feature appears to be limited to replicative polymerases of the archaeal domain...
  51. ncbi DNA polymerase-mediated DNA synthesis on a TNA template
    John C Chaput
    Howard Hughes Medical Institute, and Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    J Am Chem Soc 125:856-7. 2003
    ..We report that despite having a repeating unit that is one atom shorter than that of DNA, several polymerases showed surprisingly good ability to copy limited stretches of TNA...
  52. pmc Coordinating DNA replication by means of priming loop and differential synthesis rate
    Manjula Pandey
    Department of Biochemistry, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
    Nature 462:940-3. 2009
    ....
  53. ncbi Human homolog of the MutY repair protein (hMYH) physically interacts with proteins involved in long patch DNA base excision repair
    A Parker
    Department of Biochemistry and Molecular Biology, The University of Maryland, Baltimore, Maryland 21201, USA
    J Biol Chem 276:5547-55. 2001
    ..The PCNA- and RPA-binding sites of hMYH are further confirmed by peptide and antibody titration. These results suggest that hMYH repair is a long patch base excision repair pathway...
  54. pmc DNA interstrand crosslink repair during G1 involves nucleotide excision repair and DNA polymerase zeta
    Sovan Sarkar
    Cancer Research UK Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
    EMBO J 25:1285-94. 2006
    ..We show that this combination of NER and TLS is the only pathway of ICL repair available to the cell in G1 phase and is essential for viability in the presence of DNA crosslinks...
  55. ncbi Eukaryotic translesion synthesis DNA polymerases: specificity of structure and function
    Satya Prakash
    Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, Texas 77555 1061, USA
    Annu Rev Biochem 74:317-53. 2005
    ....
  56. ncbi A single amino acid governs enhanced activity of DinB DNA polymerases on damaged templates
    Daniel F Jarosz
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nature 439:225-8. 2006
    ....
  57. pmc Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4): an archaeal DinB-like DNA polymerase with lesion-bypass properties akin to eukaryotic poleta
    F Boudsocq
    Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, MD 20892 2725, USA
    Nucleic Acids Res 29:4607-16. 2001
    ..Thus, although phylogenetically related to DinB polymerases, our studies suggest that the archaeal Dpo4 enzyme exhibits lesion-bypass properties that are, in fact, more akin to those of eukaryotic poleta...
  58. ncbi Interactions in the error-prone postreplication repair proteins hREV1, hREV3, and hREV7
    Y Murakumo
    Department of Pathology, Nagoya University Graduate School of Medicine, 65 Tsurumai Cho, Showa Ku, Nagoya 466 8550, Japan
    J Biol Chem 276:35644-51. 2001
    ..These findings suggest the possibility that hREV7 might play an important role in regulating the enzymatic activities of hREV1 and hREV3 for mutagenesis in response to DNA damage...
  59. ncbi UBC13, a DNA-damage-inducible gene, is a member of the error-free postreplication repair pathway in Saccharomyces cerevisiae
    J Brusky
    Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, Canada
    Curr Genet 37:168-74. 2000
    ..The involvement of UBC13 in cellular tolerance to DNA-damage is further implicated by our finding that the UBC13 transcript level is increased up to 6-fold in response to DNA-damage...
  60. pmc Expression of catalytic mutants of the mtDNA helicase Twinkle and polymerase POLG causes distinct replication stalling phenotypes
    Sjoerd Wanrooij
    Institute of Medical Technology and Tampere University Hospital, Tampere, Finland
    Nucleic Acids Res 35:3238-51. 2007
    ..The observed cause-effect relationship suggests that Twinkle-induced stalling increases lagging-strand initiation events and/or maturation mimicking conventional strand-coupled replication...
  61. ncbi The mutagenesis protein UmuC is a DNA polymerase activated by UmuD', RecA, and SSB and is specialized for translesion replication
    N B Reuven
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
    J Biol Chem 274:31763-6. 1999
    ..UmuC is a member of a new family of DNA polymerases which are specialized for lesion bypass, and include the yeast RAD30 and the human XP-V genes, encoding DNA polymerase eta...
  62. pmc The accessory subunit of mitochondrial DNA polymerase gamma determines the DNA content of mitochondrial nucleoids in human cultured cells
    M Di Re
    MRC Mitochondrial Biology Unit, Wellcome Trust MRC Building, Hills Road, Cambridge, CB2 0XY, UK
    Nucleic Acids Res 37:5701-13. 2009
    ..These findings support the view that the mitochondrial D-loop acts as a protein recruitment centre, and suggest POLGbeta is a key factor in the organization of mitochondrial DNA in multigenomic nucleoprotein complexes...
  63. ncbi Differential incorporation and removal of antiviral deoxynucleotides by human DNA polymerase gamma
    S E Lim
    Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 276:23616-23. 2001
    ..Thus, although their greatest inhibitory effects are through incorporation and chain termination, persistence of these analogs in DNA and inhibition of exonucleolytic proofreading may also contribute to mitochondrial toxicity...
  64. pmc PCR amplification of DNA containing non-standard base pairs by variants of reverse transcriptase from Human Immunodeficiency Virus-1
    A Michael Sismour
    Department of Chemistry, University of Florida, Gainesville, FL 32611 7200, USA
    Nucleic Acids Res 32:728-35. 2004
    ..This work also illustrates a research strategy that combines in clinico pre-evolution of proteins followed by rational design to obtain an enzyme that meets a particular technological specification...
  65. ncbi Y-family DNA polymerases in Escherichia coli
    Daniel F Jarosz
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Trends Microbiol 15:70-7. 2007
    ..Moreover, various cellular factors can modulate their activity and mutagenic potential...
  66. pmc Identification of the epsilon-subunit of Escherichia coli DNA polymerase III holoenzyme as the dnaQ gene product: a fidelity subunit for DNA replication
    R Scheuermann
    Proc Natl Acad Sci U S A 80:7085-9. 1983
    ..We conclude that the epsilon-subunit of polymerase III holoenzyme has a special role in defining the accuracy of DNA replication, probably through control of the 3' leads to 5' exonuclease activity...
  67. ncbi Adenovirus DNA replication
    H Liu
    Centre for Biomolecular Science, Biomolecular Science Building, The University of St Andrews, North Haugh, St Andrews, KY16 9ST, UK
    Curr Top Microbiol Immunol 272:131-64. 2003
    ..Here, we discuss the role of individual proteins in this process as revealed by biochemical analysis, mutagenesis and molecular modelling...
  68. ncbi The hyperthermophilic euryarchaeota Pyrococcus abyssi likely requires the two DNA polymerases D and B for DNA replication
    Ghislaine Henneke
    IFREMER, UMR 6197, Laboratoire de Microbiologie et Environnements Extrêmes, DRV VP LM2E, BP 70, F 29280 Plouzane, France
    J Mol Biol 350:53-64. 2005
    ..Our data imply that PabPolD might play an important role in DNA replication likely together with PabpolB, suggesting that archaea require two DNA polymerases at the replication fork...
  69. pmc G-quadruplex formation within the promoter of the KRAS proto-oncogene and its effect on transcription
    Susanna Cogoi
    Department of Biomedical Science and Technology, School of Medicine, P le Kolbe 4, 33100 Udine, Italy
    Nucleic Acids Res 34:2536-49. 2006
    ..Such a mechanism, which is probably adopted by other growth-related genes, provides useful hints for the rational design of anticancer drugs against the KRAS oncogene...
  70. ncbi DNA deletions and clonal mutations drive premature aging in mitochondrial mutator mice
    Marc Vermulst
    Department of Pathology, University of Washington, Seattle, Washington 91895, USA
    Nat Genet 40:392-4. 2008
    ....
  71. ncbi Toxicity of antiviral nucleoside analogs and the human mitochondrial DNA polymerase
    A A Johnson
    Institute for Cellular and Molecular Biology, University of Texas, Austin, Texas 78712, USA
    J Biol Chem 276:40847-57. 2001
    ..We define a toxicity index for chain terminators to account for relative rates of incorporation versus removal. These results provide a method to rapidly screen new analogs for potential toxicity...
  72. ncbi Proliferating cell nuclear antigen promotes translesion synthesis by DNA polymerase zeta
    Parie Garg
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 280:23446-50. 2005
    ..However, this checkpoint clamp did not stimulate translesion synthesis by Pol zeta or by DNA polymerase delta...
  73. ncbi Reduced antigenicity of the hepatitis B virus HBsAg protein arising as a consequence of sequence changes in the overlapping polymerase gene that are selected by lamivudine therapy
    Joseph Torresi
    Department of Medicine RMH, University of Melbourne, Parkville, Victoria 3050, Australia
    Virology 293:305-13. 2002
    ..These findings raise the possibility of lamivudine-resistant mutants arising that possess antigenically distinct HBsAg proteins...
  74. pmc Analysis of equid herpesvirus 1 strain variation reveals a point mutation of the DNA polymerase strongly associated with neuropathogenic versus nonneuropathogenic disease outbreaks
    J Nugent
    Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU, United Kingdom
    J Virol 80:4047-60. 2006
    ..Strikingly, this variant amino acid occurs at a highly conserved position for herpesvirus DNA polymerases, suggesting an important functional role...
  75. pmc Targeting of human DNA polymerase iota to the replication machinery via interaction with PCNA
    L Haracska
    Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, TX 77555 1061, USA
    Proc Natl Acad Sci U S A 98:14256-61. 2001
    ..The interaction of hPoliota with PCNA implies that the targeting of this polymerase to the replication machinery stalled at a lesion site is achieved via this association...
  76. ncbi Functional analysis of multiple single-stranded DNA-binding proteins from Methanosarcina acetivorans and their effects on DNA synthesis by DNA polymerase BI
    Justin B Robbins
    Department of Animal Sciences, University of Illinois at Urbana Champaign, Urbana, Illinois 61801, USA
    J Biol Chem 279:6315-26. 2004
    ..Although bacterial SSB and eukaryotic RPA have been shown to stimulate DNA synthesis by their cognate DNA polymerases, our findings provide the first in vitro biochemical evidence for the conservation of this property in an archaeon...
  77. pmc Azathioprine and UVA light generate mutagenic oxidative DNA damage
    Peter O'Donovan
    Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
    Science 309:1871-4. 2005
    ..These findings may partly explain the prevalence of skin cancer in long-term survivors of organ transplantation...
  78. pmc Structures of phi29 DNA polymerase complexed with substrate: the mechanism of translocation in B-family polymerases
    Andrea J Berman
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
    EMBO J 26:3494-505. 2007
    ..Polymerases from the two families also interact with downstream single-stranded template DNA in very different ways...
  79. pmc 129-derived strains of mice are deficient in DNA polymerase iota and have normal immunoglobulin hypermutation
    John P McDonald
    Laboratory of Genomic Integrity, Building 6, Room 1A13, NICHD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 2725, USA
    J Exp Med 198:635-43. 2003
    ..Thus, either poliota does not participate in hypermutation, or its role is nonessential and can be readily assumed by another low-fidelity polymerase...
  80. ncbi Accelerated reaction by loop-mediated isothermal amplification using loop primers
    K Nagamine
    Eiken Chemical Co Ltd 1381 3 Shimoishigami, Ohtawara, Tochigi 324 0036, Japan
    Mol Cell Probes 16:223-9. 2002
    ..Since the total time of analysis including detection is less than 1h, this new method should facilitate genetic analysis, including genetic diagnosis in the clinical laboratory...
  81. ncbi Mutagenesis of benzo[a]pyrene diol epoxide in yeast: requirement for DNA polymerase zeta and involvement of DNA polymerase eta
    Zhongwen Xie
    Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40536, USA
    Biochemistry 42:11253-62. 2003
    ....
  82. ncbi Interaction of hREV1 with three human Y-family DNA polymerases
    Eiji Ohashi
    Institute for Virus Research, Kyoto University, 53 Shogoin Kawaracho, Sakyo ku, Kyoto 606 8507, Japan
    Genes Cells 9:523-31. 2004
    ..Thus, our results suggest that hREV1 plays a pivotal role in the multi-enzyme, multi-step process of translesion DNA synthesis...
  83. pmc Structural basis of error-prone replication and stalling at a thymine base by human DNA polymerase iota
    Kevin N Kirouac
    Department of Biochemistry, University of Western Ontario, London, Ontario, Canada
    EMBO J 28:1644-54. 2009
    ..Our structural and domain-swapping experiments indicate that the finger domain is responsible for pol's high error rates on pyrimidines and determines the incorporation specificity...
  84. ncbi How DNA lesions are turned into mutations within cells?
    Vincent Pages
    UPR 9003 du CNRS, Cancerogenese et Mutagenese Moleculaire et Structurale, UPR Conventionnee avec l Universite Louis Pasteur, ESBS, Blvd S Brant, 67400 Strasbourg, France
    Oncogene 21:8957-66. 2002
    ..We present recent aspects related to the genetics and biochemistry of TLS and highlight some of the remaining hot topics of this field...
  85. ncbi A conserved Tyr residue is required for sugar selectivity in a Pol alpha DNA polymerase
    Guangwei Yang
    Department of Molecular Biophysics and Biochemistry, Yale University, 333 Cedar Street, New Haven, Connecticut 06520, USA
    Biochemistry 41:10256-61. 2002
    ....
  86. pmc poliota, a remarkably error-prone human DNA polymerase
    A Tissier
    Section on DNA Replication, Repair, and Mutagenesis, National Institute of Child Health and Human Development, Bethesda, MD 20892 2725, USA
    Genes Dev 14:1642-50. 2000
    ..7 x 10(-1). These findings demonstrate that poliota is one of the most error-prone eukaryotic polymerases reported to date and exhibits an unusual misincorporation spectrum in vitro...
  87. ncbi POLG mutations in neurodegenerative disorders with ataxia but no muscle involvement
    G Van Goethem
    Division of Neurology and the Neuromuscular Reference Center, University Hospital, Antwerpen, Belgium
    Neurology 63:1251-7. 2004
    ..To identify POLG mutations in patients with sensory ataxia and CNS features...
  88. pmc UmuD and RecA directly modulate the mutagenic potential of the Y family DNA polymerase DinB
    Veronica G Godoy
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Mol Cell 28:1058-70. 2007
    ..Together, these observations indicate that proteins like RecA and UmuD(2) may be responsible for managing the mutagenic potential of DinB orthologs throughout evolution...
  89. ncbi Crystal structure of DNA polymerase from hyperthermophilic archaeon Pyrococcus kodakaraensis KOD1
    H Hashimoto
    Department of Materials Chemistry, Graduate School of Engineering, Osaka University, Suita, Japan
    J Mol Biol 306:469-77. 2001
    ..The stabilization of the melted DNA structure at the forked-point may be correlated with the high PCR performance of KOD DNA polymerase, which is due to low error rate, high elongation rate and processivity...
  90. ncbi Human mitochondrial DNA polymerase holoenzyme: reconstitution and characterization
    A A Johnson
    Institute for Cellular and Molecular Biology, A4800, MBB 3 122, University of Texas at Austin, Austin, Texas 78712, USA
    Biochemistry 39:1702-8. 2000
    ....
  91. ncbi Preferential misincorporation of purine nucleotides by human DNA polymerase eta opposite benzo[a]pyrene 7,8-diol 9,10-epoxide deoxyguanosine adducts
    Dominic Chiapperino
    Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 277:11765-71. 2002
    ..Mostly A was incorporated opposite (+)-BaP DE-2 dG adducts, which correlates with published observations that G --> T is the most common type of mutation that (+)-BaP DE-2 induces in mammalian cells...
  92. pmc Checkpoint activation regulates mutagenic translesion synthesis
    Mihoko Kai
    Department of Pathology, Stanford University School of Medicine, Stanford, California 94305 5324, USA
    Genes Dev 17:64-76. 2003
    ..Moreover, association of DinB with chromatin is dependent on functional Rad17, and DinB physically interacts with the checkpoint-clamp components Hus1 and Rad1. Thus, translesion synthesis is a part of the checkpoint response...
  93. ncbi Comparative kinetics of nucleotide analog incorporation by vent DNA polymerase
    Andrew F Gardner
    New England Biolabs Inc, Beverly, Massachusetts 01915, USA
    J Biol Chem 279:11834-42. 2004
    ....
  94. ncbi ATR homolog Mec1 controls association of DNA polymerase zeta-Rev1 complex with regions near a double-strand break
    Yukinori Hirano
    Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103, USA
    Curr Biol 16:586-90. 2006
    ..Our results reveal a novel role of Mec1 in the localization of the Polzeta-Rev1 complex to DNA lesions and highlight a linkage of TLS polymerases to the checkpoint response...
  95. ncbi Polymerase chain reaction and transcription using locked nucleic acid nucleotide triphosphates
    Rakesh N Veedu
    Nucleic Acid Center, Department of Physics and Chemistry, University of Southern Denmark, Campusvej 55, Odense M, 5230, Denmark
    J Am Chem Soc 130:8124-5. 2008
    ..Polymerase chain reaction amplification of a locked nucleic acid (LNA)-modified DNA strand and transcription reactions using LNA-A nucleoside 5'-triphosphate were successfully accomplished with DNA and RNA polymerases...
  96. ncbi The activity of selected RB69 DNA polymerase mutants can be restored by manganese ions: the existence of alternative metal ion ligands used during the polymerization cycle
    E Zakharova
    Department of Molecular Biophysics and Biochemistry, Yale University, 333 Cedar Street, New Haven, Connecticut 06520, USA
    Biochemistry 43:6587-95. 2004
    ..We infer that this occurs prior to the conformational change that produces the ternary RB69 pol complex in which the A and B metal ions are ligated by D623 and D411 as the enzyme is poised for phosphoryl transfer...
  97. ncbi The basic loop of the RNase H domain of MLV RT is important both for RNase H and for polymerase activity
    P L Boyer
    HIV Drug Resistance Program, National Cancer Institute-Frederick, Maryland 21702-1201, USA
    Virology 282:206-13. 2001
    ..The DeltaC mutant is impaired in both polymerase and RNase H activity; the pattern of defects suggests that the basic loop is involved in the binding of MLV RT to a heteropolymeric template-primer...
  98. pmc Physical and functional interactions of human DNA polymerase eta with PCNA
    L Haracska
    Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, Texas 77555 1061, USA
    Mol Cell Biol 21:7199-206. 2001
    ....
  99. pmc Repair of intermediate structures produced at DNA interstrand cross-links in Saccharomyces cerevisiae
    P J McHugh
    CRC Drug DNA Interactions Research Group, Department of Oncology, Royal Free and University College Medical School, University College London, London W1P 8BT, United Kingdom
    Mol Cell Biol 20:3425-33. 2000
    ....
  100. pmc Vertebrate POLQ and POLbeta cooperate in base excision repair of oxidative DNA damage
    Michio Yoshimura
    Department of Radiation Genetics, CREST, Japan Science and Technology Laboratory, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto 606 8501, Japan
    Mol Cell 24:115-25. 2006
    ..Accordingly, POLQ and POLbeta share an overlapping function in the repair of oxidative base damage. Taken together, these results suggest a role for vertebrate POLQ in BER...
  101. ncbi Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase gamma mutations
    S Winterthun
    Department of Neurology, Haukeland University Hospital, University of Bergen, Norway
    Neurology 64:1204-8. 2005
    ..To investigate three families and one sporadic case with a recessively inherited ataxic syndrome...

Research Grants65

  1. The XP Variant: A Human Mutator Gene for UV Damage
    James Cleaver; Fiscal Year: 2005
    ..We will express hRad3O on the keratin 14 promoter for over-expression in the skin, and make targeted knockout of mRad3O in vivo to identify roles for hRad3O in promoting and preventing carcinogenesis. ..
  2. MOUSE MODELS OF DNA REPAIR - DEFECTIVE HUMAN DISEASES
    Errol Friedberg; Fiscal Year: 2011
    ..abstract_text> ..
  3. DNA Damage and Neurodegeneration in Cockayne Syndrome
    James Cleaver; Fiscal Year: 2009
    ..Successful conclusion of these studies will expand our knowledge of mechanisms of neurodegeneration and lay groundwork for development of therapeutic approaches for CS patients. ..
  4. DNA-PROTEIN COMPLEX OF BACILLUS SUBTILITS PHAGE 029
    Margarita Salas; Fiscal Year: 2003
    ..subtilis RNA polymerase at promoters A3 and A2c, the switch from early to late transcription in phage GA-1, and the mechanism of p6 repression at promoters C2 and A2c. ..
  5. 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. ..
  6. DNA REPAIR AND CANCER PRONE HEREDITARY HUMAN DISEASE
    Errol Friedberg; Fiscal Year: 2002
    ....
  7. KINETIC ANALYSIS OF MICROTUBULE-DEPENDENT ATPASES
    Kenneth Johnson; Fiscal Year: 2003
    ..The combination of approaches outlined here will provide rigorous and direct information to define the structural and mechanistic basis for force production by kinesin. ..
  8. RE-ENGINEERING THE DIAMETER OF THE DOULBE HELIX
    Eric T Kool; Fiscal Year: 2010
    ..Finally, we will study basic biophysical, structuraland thermodynamic properties of these compounds, to better understandand delineate their utility as broadly applicable tools. ..
  9. CHEMICAL AND BIOLOGICAL MIMICRY OF TELOMERASE
    ERIC KOOL; Fiscal Year: 2007
    ..Chemical approaches to telomere elongation have the long-term potential to solve important problems in transplantation medicine, and to lead to new treatments for senescence-related diseases. ..
  10. Elementary Steps in DNA Polymerization
    Kenneth Johnson; Fiscal Year: 2008
    ..abstract_text> ..
  11. NOVEL PROBE TOPOLOGIES IN BIOMEDICAL DIAGNOSTICS
    ERIC KOOL; Fiscal Year: 2002
    ..Over the long term, it is hoped that this approach will give rise to clinically useful methods for the early diagnosis of diseases. ..
  12. NONPOLAR NUCLEOSIDE ISOSTERES AS BIOMOLECULAR PROBES
    ERIC KOOL; Fiscal Year: 2003
    ..abstract_text> ..
  13. PURCHASE OF A VARIAN INOVA 600 MHz NMR SPECTROMETER
    ERIC KOOL; Fiscal Year: 2002
    ..1 T magnet, as well as supershims, two Fullband RF channels with three total RF channels, waveform generators for each channel, a variable temperature unit, pulsed field gradients, a Sun workstation, and a cryo probe. ..
  14. NONPOLAR NUCLEOSIDE ISOSTERES AS BIOMOLECULAR PROBES
    ERIC KOOL; Fiscal Year: 2002
    ..abstract_text> ..
  15. CREATING MUTANT ENZYMES FOR GENE THERAPY OF CANCER
    LAWRENCE LOEB; Fiscal Year: 2007
    ..abstract_text> ..
  16. Regulation of DNA Replication and Repair
    Mark Sutton; Fiscal Year: 2008
    ..abstract_text> ..
  17. HUMAN V(D)J RECOMBINASE IN NEOPLASTIC AND PRIMARY CELLS
    Michael Lieber; Fiscal Year: 2004
    ..Corresponding studies of such regions on minichromosomes will permit the testing of the effects of the direction of DNA replication and transcription. ..
  18. 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. ..
  19. OXYGEN INDUCED DNA DAMAGE, MUTATIONS AND CANCER
    LAWRENCE LOEB; Fiscal Year: 2003
    ..Even a modest, 2-fold, decrease could increase the latent period before disease is manifested clinically and thus reduce cancer mortality. ..
  20. 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. ..
  21. LETHAL MUTAGENESIS OF HIV BY DEOXYNUCLEOSIDE ANALOGS
    LAWRENCE LOEB; Fiscal Year: 2002
    ....
  22. EVOLUTION OF THE RIBONUCLEASE SUPERFAMILY
    Steven Benner; Fiscal Year: 2001
    ....
  23. Universal Technology for Profiling the Dynamics of Normal & Oncogenic Signaling
    Karen Anderson; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  24. Artificial Genetic Systems
    Steven A Benner; Fiscal Year: 2010
    ..Multiplexed PCR is the rate limiting step in many genomics analyses. Our long term, highly ambitious goal is to develop a "synthetic biology", a chemical system capable of Darwinian evolution, based on AEGIS components. ..
  25. Polymerases for Sequencing by Synthesis
    Steven Benner; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  26. Novel Approach to Study Transient Enzyme Intermediates
    Karen Anderson; Fiscal Year: 2008
    ..These studies will aid in pioneering a powerful and novel analytical methodology for detecting, characterizing and quantitating enzyme intermediates on a rapid time scale. ..
  27. Bacterial cell cycle control
    SUSAN THOMAS LOVETT; Fiscal Year: 2010
    ..LAY DESCRIPTION: We will study a protein present in all bacteria that appears to control their growth. This will provide important missing information about how bacteria divide and may provide a target for antibiotics. ..
  28. A Molecular Approach For Opportunistic HIV-1 Infections
    Karen Anderson; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  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. MECHANISTIC STUDIES ON PEP UTILIZING ENZYMES
    Karen Anderson; Fiscal Year: 2003
    ..In addition as the investigator develops the quantitative aspects of the rapid mixing, pulsed-flow ESI-MS technique further, she will extend the studies of these enzymes to determine the full kinetic profile. ..
  31. NUCLEASES IN DNA REPAIR AND RECOMBINATION
    SUSAN LOVETT; Fiscal Year: 2006
    ..We will extend genetic analysis of radC to determine what role it may play in repair and recombination. ..
  32. DNA Sequencing using Nanopores
    Steven Benner; Fiscal Year: 2007
    ..These will then be targeted against specific sequences extracted from mammalian genomes. [unreadable] [unreadable]..
  33. ROS-induced Nucleic Acid Damage
    Yinsheng Wang; Fiscal Year: 2006
    ..The outcome of the research proposed here will provide better understanding of the biological consequences of oxidative damage on nucleic acids by ROS and their implications in human health. ..
  34. Near Term Development of Reagents and Enzymes for Genome Sequencing
    Steven A Benner; Fiscal Year: 2010
    ..This proposal, from a laboratory with a track record of innovation in structures, reagents, and enzymes to manipulate nucleic acids, is focused on near term development of these to enable NHGRI cost-reduction sequencing goals. ..
  35. NON-STANDARD BASE PAIRS AS BIOMEDICAL RESEARCH TOOLS
    Steven Benner; Fiscal Year: 2004
    ....
  36. Post-translational Modifications of High-mobility Group Proteins
    Yinsheng Wang; Fiscal Year: 2009
    ..In addition, the outcome of proposed studies may provide important molecular biomarkers for cancer diagnosis and prognosis. ..
  37. Dynamic combinatorial chemistry for nucleic acids
    Steven Benner; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  38. CLINICAL RESEARCH CENTER FOR NEUROMUSCULAR DISEASE
    Salvatore DiMauro; Fiscal Year: 2007
    ....
  39. Targeted Assisted Combinational Synthesis
    Steven Benner; Fiscal Year: 2004
    ..abstract_text> ..
  40. Effects of Formamidopyrimidine Lesions on DNA
    Marc Greenberg; Fiscal Year: 2006
    ..abstract_text> ..
  41. Single-particle fluorescence studies of viral fusion
    Antoine Van Oijen; Fiscal Year: 2008
    ..The proposed development and use of single-particle imaging techniques to study the fusion mechanism of influenza will lead to a more complete and dynamic picture of the various pathways involved. ..
  42. Error Prone DNA Synthesis and Oncogene Mutagensis
    Bernard Strauss; Fiscal Year: 2004
    ..Blocking the action of the error-prone polymerases should not stop replication. However, mutational cascades, such as those leading to tumor drug resistance, should be inhibited by such a block. ..
  43. Repair of Clustered DNA Damages
    Yoke W Kow; Fiscal Year: 2010
    ..In addition, it will provide significant insight as to the potential mechanism involved in melanoma progression. ..
  44. Mitochondria and Carcinogenesis
    Keshav K Singh; Fiscal Year: 2010
    ..The proposed study will help determine the contribution of mutant mtDNA to the development of human cancer. ..
  45. MUTATIONAL MECHANISMS OF REPETITIVE DNA IN HUMAN CELLS
    Kristin Eckert; Fiscal Year: 2001
    ..Our long-term research objective is to test the hypothesis that mutations in repetitive DNA provide an important source of genotypic variation that drives neoplastic progression. ..
  46. MECHANISMS REGULATING HSV TK EXPRESSION DURING INFECTION
    Donald M Coen; Fiscal Year: 2010
    ..The relevance of these three aims for public health is that they explore gene regulatory mechanisms important for disease and for resistance of pathogens to antiviral drugs. ..
  47. HYBRID MOLECULES DESIGNED TO ENHANCE ANTIBIOTIC ACTIVITY
    George Wright; Fiscal Year: 2003
    ..abstract_text> ..
  48. Immunoglobulin class switch DNA recombination
    Paolo Casali; Fiscal Year: 2011
    ..abstract_text> ..
  49. Targeting Tumor Angiogenesis with G-Quadruplex Binders
    Daekyu Sun; Fiscal Year: 2010
    ..abstract_text> ..
  50. Mechanism and in vivo anti-HBV study of a novel class of non-nucleoside compounds
    Yung Chi Cheng; Fiscal Year: 2010
    ..The studies proposed will provide information about not only the potential of the novel compound 8-1, as an anti-HBV drug, but also the roles of liver enriched transcription factors in regulation of HBV transcription. ..
  51. Mitochondria and Mutagenesis
    Keshav K Singh; Fiscal Year: 2010
    ..abstract_text> ..
  52. Methyl selenium regulation of Angiogenic switch Mech
    Junxuan Lu; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  53. Gordon Research Conference on Mutagenesis, 2002
    MYRON GOODMAN; Fiscal Year: 2002
    ..abstract_text> ..
  54. Signaling by the ATM and ATR Kinases
    David Cortez; Fiscal Year: 2006
    ..The award will facilitate the candidate's transition from a mentored research environment to an independent academic research position focused on basic cancer biology. ..
  55. Viral Etiology of Kaposi's sarcoma-like Tumors
    TIMOTHY ROSE; Fiscal Year: 2005
    ..Additional training and focused research in virology would allow Dr. Rose to expand upon his initial discovery and make further significant contributions in the fields of herpesviruses and viral pathogenicity. ..
  56. Profiles of Sucsceptibility to Toxicant Stress
    William Kaufmann; Fiscal Year: 2007
    ..The UNC-CH toxicogenomics research program has the scientific expertise and organizational infrastructure to provide significant and substantial benefits to the Toxicogenomics Research Consortium. ..
  57. DYNAMICS OF PROTEIN-DNA INTERACTIONS IN DNA REPLICATION
    LINDA BLOOM; Fiscal Year: 2008
    ..coli system and many analogies are seen in the human system. An E. coil model system offers the advantage that stable proteins can be obtained in high yields for in vitro analysis. ..
  58. Evolving Novel Polymerases for Genome Sequencing
    FLOYD ROMESBERG; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  59. NUCLEOSIDE ANALOGS AS ANTICANCER COMPOUNDS
    Yung Chi Cheng; Fiscal Year: 2007
    ..It should yield novel information for understanding the biochemical determinants of the action of L-OddC, the biochemistry of the enzymes studied and possible novel use of L-OddC for the treatment of solid tumor. ..
  60. Specificity and Structure: The Kex 2 and Furin Proteases
    Robert Fuller; Fiscal Year: 2005
    ..2. To elucidate the biochemistry and physiology of processing of yeast cell wall proteins by Kex2p and GPI-anchored aspartyl proteases. 3. To achieve Kex2p and furin crystallization to advance determination of their structures. ..
  61. Gene Duplication and Genome Evolution
    Austin Hughes; Fiscal Year: 2004
    ..5) Examining the role of transposable elements in duplication of genomic segments by testing for nonrandom association between these elements and putatively duplicated blocks in the yeast genome. ..
  62. DEVELOPMENT OF A LIVE ATTENUATED HSV-2 VACCINE
    Mark Prichard; Fiscal Year: 2002
    ..In addition further in vitro characterization will enable high quality clinical trial material to be produced for IND enabling primate studies and early Phase I human trials. PROPOSED COMMERCIAL APPLICATION: Not Available ..
  63. DNA LIGASE I AS A POTENTIAL TARGET FOR ANTICANCER DRUGS
    Daekyu Sun; Fiscal Year: 2002
    ..3) Test whether DNA ligase I inhibition produces antitumor activity using antisense strategy in preclinical in vitro and in vivo evaluation systems. 4) Develop a sensitive and reproducible assay for DNA ligase I. ..
  64. Abnormalities/Signal Transduction/Hematopoietic Disease
    ALAN D ANDREA; Fiscal Year: 2006
    ..abstract_text> ..