dna polymerase beta

Summary

Summary: A DNA repair enzyme that catalyzes DNA synthesis during base excision DNA repair. EC 2.7.7.7.

Top Publications

  1. doi Structural insight into recruitment of translesion DNA polymerase Dpo4 to sliding clamp PCNA
    Guangxin Xing
    Department of Biochemistry, University of Western Ontario, London, Ontario, Canada
    Mol Microbiol 71:678-91. 2009
  2. pmc XRCC1 is specifically associated with poly(ADP-ribose) polymerase and negatively regulates its activity following DNA damage
    M Masson
    UPR 9003 du Centre National de la Recherche Scientifique, Cancerogenese et Mutagenese Moleculaire et Structurale, Ecole Superieure de Biotechnologie de Strasbourg, 67400 Illkirch Graffenstaden, France
    Mol Cell Biol 18:3563-71. 1998
  3. pmc DNA polymerase beta ribonucleotide discrimination: insertion, misinsertion, extension, and coding
    Nisha A Cavanaugh
    Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709 2233, USA
    J Biol Chem 285:24457-65. 2010
  4. pmc Stoichiometry of base excision repair proteins correlates with increased somatic CAG instability in striatum over cerebellum in Huntington's disease transgenic mice
    Agathi Vassiliki Goula
    Department of Neurobiology and Genetics, Institute of Genetics and Molecular and Cellular Biology, UMR 7104 CNRS INSERM UdS, Illkirch, France
    PLoS Genet 5:e1000749. 2009
  5. ncbi AP endonuclease-independent DNA base excision repair in human cells
    Lee Wiederhold
    Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77555, USA
    Mol Cell 15:209-20. 2004
  6. pmc DNA base excision repair: a mechanism of trinucleotide repeat expansion
    Yuan Liu
    Department of Chemistry and Biochemistry, Florida International University, Miami, FL 33199, USA
    Trends Biochem Sci 37:162-72. 2012
  7. 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
  8. pmc N-methylpurine DNA glycosylase and DNA polymerase beta modulate BER inhibitor potentiation of glioma cells to temozolomide
    Jiang bo Tang
    Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    Neuro Oncol 13:471-86. 2011
  9. pmc Escherichia coli DNA polymerase IV mutator activity: genetic requirements and mutational specificity
    J Wagner
    Division of Genetics and Mutagenesis, National Institute of Health Sciences, Setagaya Ku, Tokyo 158 8501, Japan
    J Bacteriol 182:4587-95. 2000
  10. pmc Human DNA polymerase beta polymorphism, Arg137Gln, impairs its polymerase activity and interaction with PCNA and the cellular base excision repair capacity
    Zhigang Guo
    Department of Radiation Biology, City of Hope National Medical Center, Beckman Research Institute, Duarte, CA 91010, USA
    Nucleic Acids Res 37:3431-41. 2009

Detail Information

Publications256 found, 100 shown here

  1. doi Structural insight into recruitment of translesion DNA polymerase Dpo4 to sliding clamp PCNA
    Guangxin Xing
    Department of Biochemistry, University of Western Ontario, London, Ontario, Canada
    Mol Microbiol 71:678-91. 2009
    ....
  2. pmc XRCC1 is specifically associated with poly(ADP-ribose) polymerase and negatively regulates its activity following DNA damage
    M Masson
    UPR 9003 du Centre National de la Recherche Scientifique, Cancerogenese et Mutagenese Moleculaire et Structurale, Ecole Superieure de Biotechnologie de Strasbourg, 67400 Illkirch Graffenstaden, France
    Mol Cell Biol 18:3563-71. 1998
    ..Given that XRCC1 is also associated with DNA ligase III via a second BRCT module and with DNA polymerase beta, our results provide strong evidence that PARP is a member of a BER multiprotein complex involved in the ..
  3. pmc DNA polymerase beta ribonucleotide discrimination: insertion, misinsertion, extension, and coding
    Nisha A Cavanaugh
    Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709 2233, USA
    J Biol Chem 285:24457-65. 2010
    ..Here, we investigate the ability of DNA polymerase beta to utilize nucleotides with modified sugars...
  4. pmc Stoichiometry of base excision repair proteins correlates with increased somatic CAG instability in striatum over cerebellum in Huntington's disease transgenic mice
    Agathi Vassiliki Goula
    Department of Neurobiology and Genetics, Institute of Genetics and Molecular and Cellular Biology, UMR 7104 CNRS INSERM UdS, Illkirch, France
    PLoS Genet 5:e1000749. 2009
    ..We propose that the stoichiometry of BER enzymes is one critical factor underlying the tissue selectivity of somatic CAG expansion...
  5. ncbi AP endonuclease-independent DNA base excision repair in human cells
    Lee Wiederhold
    Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77555, USA
    Mol Cell 15:209-20. 2004
    ..NEIL1 stably interacts with other BER proteins, DNA polymerase beta (pol beta) and DNA ligase IIIalpha...
  6. pmc DNA base excision repair: a mechanism of trinucleotide repeat expansion
    Yuan Liu
    Department of Chemistry and Biochemistry, Florida International University, Miami, FL 33199, USA
    Trends Biochem Sci 37:162-72. 2012
    ....
  7. 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
    ....
  8. pmc N-methylpurine DNA glycosylase and DNA polymerase beta modulate BER inhibitor potentiation of glioma cells to temozolomide
    Jiang bo Tang
    Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    Neuro Oncol 13:471-86. 2011
    ....
  9. pmc Escherichia coli DNA polymerase IV mutator activity: genetic requirements and mutational specificity
    J Wagner
    Division of Genetics and Mutagenesis, National Institute of Health Sciences, Setagaya Ku, Tokyo 158 8501, Japan
    J Bacteriol 182:4587-95. 2000
    ..These results are discussed with respect to the recently described biochemical characteristics of DNA Pol IV...
  10. pmc Human DNA polymerase beta polymorphism, Arg137Gln, impairs its polymerase activity and interaction with PCNA and the cellular base excision repair capacity
    Zhigang Guo
    Department of Radiation Biology, City of Hope National Medical Center, Beckman Research Institute, Duarte, CA 91010, USA
    Nucleic Acids Res 37:3431-41. 2009
    b>DNA polymerase beta (Pol beta) is a key enzyme in DNA base excision repair, and an important factor for maintaining genome integrity and stability...
  11. 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
    ....
  12. pmc In situ analysis of repair processes for oxidative DNA damage in mammalian cells
    Li Lan
    Department of Molecular Genetics, Institute of Development, Aging, and Cancer, Tohoku University, Seiryomachi 4 1, Sendai 980 8575, Japan
    Proc Natl Acad Sci U S A 101:13738-43. 2004
    ..Furthermore, we characterized repair pathways by using repair-defective mammalian cells and found that DNA polymerase beta accumulated at single-strand breaks and oxidative base damage by means of its 31- and 8-kDa domains, ..
  13. pmc Coordination between polymerase beta and FEN1 can modulate CAG repeat expansion
    Yuan Liu
    Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 284:28352-66. 2009
    ..This is the first report illustrating that disruption of pol beta and FEN1 coordination during long-patch BER results in CAG repeat expansion...
  14. ncbi A physical and functional interaction between yeast Pol4 and Dnl4-Lif1 links DNA synthesis and ligation in nonhomologous end joining
    Hui Min Tseng
    Department of Molecular Medicine and Institute of Biotechnology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78245 3207, USA
    J Biol Chem 277:45630-7. 2002
    ....
  15. pmc An 8-oxo-guanine repair pathway coordinated by MUTYH glycosylase and DNA polymerase lambda
    Barbara van Loon
    Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
    Proc Natl Acad Sci U S A 106:18201-6. 2009
    ..These results reveal a cellular response pathway to ROS, important to sustain genomic stability and modulate carcinogenesis...
  16. pmc A novel mechanism of sugar selection utilized by a human X-family DNA polymerase
    Jessica A Brown
    Department of Biochemistry, The Ohio State University, Columbus, OH 43210, USA
    J Mol Biol 395:282-90. 2010
    ..Such steric clash was further demonstrated to be dependent on the size and orientation of the substituent covalently attached at the ribonucleotide C2'-position...
  17. ncbi SOS mutator DNA polymerase IV functions in adaptive mutation and not adaptive amplification
    G J McKenzie
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030 3411, USA
    Mol Cell 7:571-9. 2001
    ..We show that pol IV, together with the major replicase, pol III, can account for all adaptive point mutations at lac. The results identify a role for pol IV in inducible genetic change...
  18. pmc Control of DNA polymerase lambda stability by phosphorylation and ubiquitination during the cell cycle
    Ursula Wimmer
    Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Switzerland
    EMBO Rep 9:1027-33. 2008
    ..In particular, Pol lambda is stabilized during cell cycle progression in the late S and G2 phases. This most likely allows Pol lambda to correctly conduct repair of damaged DNA during and after S phase...
  19. ncbi DNA polymerases beta and lambda bypass thymine glycol in gapped DNA structures
    Ekaterina A Belousova
    Institute of Chemical Biology and Fundamental Medicine, SB RAS, Novosibirsk, Russia
    Biochemistry 49:4695-704. 2010
    ..fidelity of Tg bypass and does not influence normal DNA synthesis catalyzed by DNA polymerase lambda, (iv) DNA polymerase beta catalyzes the incorporation of all four dNTPs opposite Tg, and (v) hPCNA as well as hRPA has no specific ..
  20. ncbi Local deformations revealed by dynamics simulations of DNA polymerase Beta with DNA mismatches at the primer terminus
    Linjing Yang
    Department of Chemistry and Courant Institute of Mathematical Sciences, New York University and the Howard Hughes Medical Institute, 251 Mercer Street, 10012, New York, NY, USA
    J Mol Biol 321:459-78. 2002
    Nanosecond dynamics simulations for DNA polymerase beta (pol beta)/DNA complexes with three mismatched base-pairs, namely GG, CA, or CC (primer/template) at the DNA polymerase active site, are performed to investigate the mechanism of ..
  21. doi Modulation of DNA polymerase beta-dependent base excision repair in cultured human cells after low dose exposure to arsenite
    Peter Sykora
    Centre for Cellular and Molecular Biology, School of Biological Sciences, Deakin University, Australia
    Toxicol Appl Pharmacol 228:385-94. 2008
    ..To address this question we have investigated the regulation of DNA polymerase beta (Pol beta) and AP endonuclease (APE1), in response to low, physiologically relevant doses of arsenic...
  22. doi Mechanism of error-free and semitargeted mutagenic bypass of an aromatic amine lesion by Y-family polymerase Dpo4
    Olga Rechkoblit
    Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA
    Nat Struct Mol Biol 17:379-88. 2010
    ..Further extension leads to semitargeted mutations via this proposed polymerase-guided mechanism...
  23. pmc XRCC1 and DNA polymerase beta in cellular protection against cytotoxic DNA single-strand breaks
    Julie K Horton
    Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Cell Res 18:48-63. 2008
    ..A requirement for the deoxyribose phosphate lyase activity of DNA polymerase beta (pol beta) is specific to this pathway, whereas pol beta is implicated in gap-filling during repair of many ..
  24. pmc Substrate channeling in mammalian base excision repair pathways: passing the baton
    Rajendra Prasad
    Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 285:40479-88. 2010
    ..Instead, flap endonuclease 1 must recognize and bind to the intermediate in competition with other molecules...
  25. pmc DNA polymerases beta and lambda mediate overlapping and independent roles in base excision repair in mouse embryonic fibroblasts
    Elena K Braithwaite
    Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, United States of America
    PLoS ONE 5:e12229. 2010
    ..While DNA polymerase beta (pol beta) is known to be the main polymerase in the BER pathway, various studies have implicated other DNA ..
  26. ncbi DNA polymerase beta and flap endonuclease 1 enzymatic specificities sustain DNA synthesis for long patch base excision repair
    Yuan Liu
    Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 280:3665-74. 2005
    b>DNA polymerase beta (pol beta) and flap endonuclease 1 (FEN1) are key players in pol beta-mediated long-patch base excision repair (LP-BER)...
  27. 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...
  28. pmc Replication protein A and proliferating cell nuclear antigen coordinate DNA polymerase selection in 8-oxo-guanine repair
    Giovanni Maga
    Institute of Molecular Genetics, Consiglio Nazionale delle Ricerche, via Abbiategrasso 207, I 27100 Pavia, Italy
    Proc Natl Acad Sci U S A 105:20689-94. 2008
    ....
  29. ncbi Direct interaction between mammalian DNA polymerase beta and proliferating cell nuclear antigen
    Padmini S Kedar
    Laboratory of Structural Biology, NIEHS National Institutes of Health, 111 T W Alexander Drive, Research Triangle Park, NC 27709, USA
    J Biol Chem 277:31115-23. 2002
    ..The results indicate that at least one of the PIM-like sequences in beta-polymerase appears to be a functional PIM and was required in the interaction between beta-polymerase and PCNA...
  30. pmc Role of the catalytic metal during polymerization by DNA polymerase lambda
    Miguel Garcia-Diaz
    Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA
    DNA Repair (Amst) 6:1333-40. 2007
    ..These data provide pre- and post-transition state information and outline in a single crystal the pathway for the phosphoryl transfer reaction carried out by DNA polymerases...
  31. pmc Structures of DNA polymerase beta with active-site mismatches suggest a transient abasic site intermediate during misincorporation
    Vinod K Batra
    Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, P O Box 12233, Research Triangle Park, NC 27709, USA
    Mol Cell 30:315-24. 2008
    We report the crystallographic structures of DNA polymerase beta with dG-dAMPCPP and dC-dAMPCPP mismatches in the active site...
  32. ncbi 8-oxodGTP incorporation by DNA polymerase beta is modified by active-site residue Asn279
    H Miller
    Department of Pharmacological Sciences, SUNY Stony Brook, Stony Brook, New York 11794 8651, USA
    Biochemistry 39:1029-33. 2000
    ..of 8-oxo-7,8-dihydrodeoxyguanine (8-oxodG), we performed steady-state kinetic analyses using wild-type DNA polymerase beta (pol beta) and two active-site mutants...
  33. pmc The checkpoint clamp, Rad9-Rad1-Hus1 complex, preferentially stimulates the activity of apurinic/apyrimidinic endonuclease 1 and DNA polymerase beta in long patch base excision repair
    Agnieszka Gembka
    Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich Irchel, Winterthurerstrasse 190, CH 8057, Zurich, Switzerland
    Nucleic Acids Res 35:2596-608. 2007
    ..and functionally interacts with several components of the base excision repair (BER) machinery namely DNA polymerase beta (Pol beta), flap endonuclease 1 (Fen 1), DNA ligase I (Lig I) and the MutY homologue of Schizosaccharomyces ..
  34. pmc Error-prone DNA polymerase IV is controlled by the stress-response sigma factor, RpoS, in Escherichia coli
    Jill C Layton
    Department of Biology, Indiana University, Bloomington, IN 47405, USA
    Mol Microbiol 50:549-61. 2003
    ..Even in cells missing LexA, the repressor of dinB, maximum Pol IV expression required RpoS. These results suggest that induction of Pol IV is part of a cellular response to starvation and other stresses...
  35. ncbi Misalignment-mediated DNA polymerase beta mutations: comparison of microsatellite and frame-shift error rates using a forward mutation assay
    Kristin A Eckert
    Department of Pathology, Gittlen Cancer Research Institute, The Pennsylvania State University College of Medicine, Hershey Medical Center, 500 University Drive, Hershey, Pennsylvania 17033, USA
    Biochemistry 41:10490-8. 2002
    ..To our knowledge, this is the first direct quantitation of DNA polymerase errors in vitro using template microsatellite sequences...
  36. 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...
  37. ncbi A role for DNA polymerase beta in mutagenic UV lesion bypass
    Laurence Servant
    Group Genetic instability and cancer at the Institut de Pharmacologie et Biologie Structurale, UMR CNRS 5089, 31077 Toulouse Cedex 4, France
    J Biol Chem 277:50046-53. 2002
    We report here that DNA polymerase beta (pol beta), the base excision repair polymerase, is highly expressed in human melanoma tissues, known to be associated with UV radiation exposure...
  38. ncbi Polymorphisms of the DNA polymerase beta gene in breast cancer
    Tomasz Sliwinski
    Department of Molecular Genetics, University of Lodz, Banacha 12 16, Lodz, 90 237, Poland
    Breast Cancer Res Treat 103:161-6. 2007
    b>DNA polymerase beta (Polbeta) provides most of the gap-filling synthesis at apurinic/apyrimidine sites of damaged DNA in the base excision repair pathway...
  39. pmc In silico evidence for DNA polymerase-beta's substrate-induced conformational change
    Karunesh Arora
    Department of Chemistry and Courant Institute of Mathematical Sciences, New York University, New York, New York 10012, USA
    Biophys J 87:3088-99. 2004
    ..Further details gleaned from essential dynamics analyses clarify functionally relevant global motions of the polymerase-beta/DNA complex as required to prepare the system for the chemical reaction of nucleotide extension...
  40. pmc Molecular insights into DNA polymerase deterrents for ribonucleotide insertion
    Nisha A Cavanaugh
    Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709 2233, USA
    J Biol Chem 286:31650-60. 2011
    ..Our results support a model where DNA polymerase β utilizes two strategies, steric and geometric, with a single protein residue to deter ribonucleotide insertion...
  41. pmc Saccharomyces cerevisiae Sae2- and Tel1-dependent single-strand DNA formation at DNA break promotes microhomology-mediated end joining
    Kihoon Lee
    Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245, USA
    Genetics 176:2003-14. 2007
    ..Sae2 and Tel1 promote MMEJ but inhibit NHEJ, likely by regulating Mre11-dependent ssDNA accumulation at DNA break. Our data support the role of Sae2 and Tel1 in MMEJ and genome integrity...
  42. ncbi Cells deficient in the base excision repair protein, DNA polymerase beta, are hypersensitive to oxaliplatin chemotherapy
    J Yang
    Cancer Research UK Medical Research Council Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford, Oxon OX37DQ, UK
    Oncogene 29:463-8. 2010
    A significant proportion of human cancers overexpress DNA polymerase beta (Pol beta), the major DNA polymerase involved in base excision repair...
  43. pmc DNA polymerase beta is critical for mouse meiotic synapsis
    Dawit Kidane
    Department of Therapeutic Radiology, The Yale Comprehensive Cancer Center, New Haven, CT, USA
    EMBO J 29:410-23. 2010
    We have shown earlier that DNA polymerase beta (Pol beta) localizes to the synaptonemal complex (SC) during Prophase I of meiosis in mice...
  44. ncbi Efficiency of correct nucleotide insertion governs DNA polymerase fidelity
    William A Beard
    Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 277:47393-8. 2002
    ..An analysis of the efficiency of dNTP (correct and incorrect) insertion for a low fidelity mutant of DNA polymerase beta (R283A) and exonuclease-deficient DNA polymerases from five families derived from a variety of biological ..
  45. ncbi De novo DNA synthesis by human DNA polymerase lambda, DNA polymerase mu and terminal deoxyribonucleotidyl transferase
    Kristijan Ramadan
    Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich Irchel, Winterthurerstrasse 190, CH 8057, Zurich, Switzerland
    J Mol Biol 339:395-404. 2004
    ..This novel catalytic activity might be related to the proposed functions of these three pol X family members in DNA repair and DNA recombination...
  46. pmc Folate deficiency provides protection against colon carcinogenesis in DNA polymerase beta haploinsufficient mice
    Lisa F Ventrella-Lucente
    Department of Nutrition and Food, Science College of Liberal Arts and Sciences, School of Medicine, Wayne State University, Detroit, Michigan 48202, USA
    J Biol Chem 285:19246-58. 2010
    Aging and DNA polymerase beta deficiency (beta-pol(+/-)) interact to accelerate the development of malignant lymphomas and adenocarcinoma and increase tumor bearing load in mice...
  47. pmc Differing conformational pathways before and after chemistry for insertion of dATP versus dCTP opposite 8-oxoG in DNA polymerase beta
    Yanli Wang
    Department of Chemistry and Courant Institute of Mathematical Sciences, New York University, New York, New York, USA
    Biophys J 92:3063-70. 2007
    To elucidate how human DNA polymerase beta (pol beta) discriminates dATP from dCTP when processing 8-oxoguanine (8-oxoG), we analyze a series of dynamics simulations before and after the chemical step with dATP and dCTP opposite an 8-..
  48. ncbi Influence of DNA structure on DNA polymerase beta active site function: extension of mutagenic DNA intermediates
    William A Beard
    Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 279:31921-9. 2004
    ....
  49. pmc The E295K DNA polymerase beta gastric cancer-associated variant interferes with base excision repair and induces cellular transformation
    Tieming Lang
    Department of Therapeutic Radiology, Yale University School of Medicine, 15 York Street, P O Box 20840, New Haven, CT 06520, USA
    Mol Cell Biol 27:5587-96. 2007
    ..The results indicate that base excision repair is critical for maintaining genome stability and could therefore be a tumor suppressor mechanism...
  50. ncbi Marine sesquiterpenoids that inhibit the lyase activity of DNA polymerase beta
    Shugeng Cao
    Department of Chemistry, M C 0212, Virginia Polytechnic Institute and State University, Blacksburg 24061, USA
    J Nat Prod 67:1716-8. 2004
    ..The structure of the new compound 1 was determined on the basis of spectroscopic methods and by conversion of dictyoceratin-C (2) to 1...
  51. pmc Magnesium-cationic dummy atom molecules enhance representation of DNA polymerase beta in molecular dynamics simulations: improved accuracy in studies of structural features and mutational effects
    Peter Oelschlaeger
    University of Southern California, Department of Chemistry, Los Angeles, CA 90089 1062, USA
    J Mol Biol 366:687-701. 2007
    Human DNA polymerase beta (pol beta) fills gaps in DNA as part of base excision DNA repair. Due to its small size it is a convenient model enzyme for other DNA polymerases...
  52. ncbi DNA repair in aging rat neurons
    K Subba Rao
    ICMR Advanced Center for Research on Aging and Brain, Department of Biochemistry, School of Life Sciences, University of Hyderabad, Gachibowli, Hyderabad, Andhra Pradesh 500 046, India
    Neuroscience 145:1330-40. 2007
    ..The extension activity could be restored by supplementing the neuronal extracts with pure DNA polymerase beta (pol beta) while the restoration of gap repair needed the addition of both pol beta and DNA ligase...
  53. pmc DNA polymerase beta substrate specificity: side chain modulation of the "A-rule"
    William A Beard
    Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 284:31680-9. 2009
    ..Thus, dATP insertion opposite an abasic site and dATP misinsertions have common features...
  54. pmc Y265C DNA polymerase beta knockin mice survive past birth and accumulate base excision repair intermediate substrates
    Alireza G Senejani
    Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 109:6632-7. 2012
    ..DNA polymerase β is known to be a key player in the base excision repair pathway, and mice devoid of DNA polymerase beta do not live beyond a few hours after birth...
  55. ncbi Genetic interaction between DNA polymerase beta and DNA-PKcs in embryogenesis and neurogenesis
    N Niimi
    Kihara Institute for Biological Research and Graduate School of Integrated Science, Yokohama City University, 641 12 Maioka cho, Totsuka ku, Yokohama 244 0813, Japan
    Cell Death Differ 12:184-91. 2005
    b>DNA polymerase beta (Polbeta) has been implicated in base excision repair. Polbeta knockout mice exhibit apoptosis in postmitotic neuronal cells and die at birth...
  56. pmc Long patch base excision repair proceeds via coordinated stimulation of the multienzyme DNA repair complex
    Lata Balakrishnan
    Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
    J Biol Chem 284:15158-72. 2009
    ..repair sub-pathway (LP-BER), including DNA glycosylases, apurinic/apyrimidinic endonuclease 1 (APE1), DNA polymerase beta (pol beta), flap endonuclease 1 (FEN1), and DNA ligase I (LigI)...
  57. ncbi Roles of chromosomal and episomal dinB genes encoding DNA pol IV in targeted and untargeted mutagenesis in Escherichia coli
    S R Kim
    Mol Genet Genomics 266:207-15. 2001
    ..These results suggest that DNA pol IV efficiently mediates targeted mutagenesis by 4-NQO, and that the cellular levels of expression substantially affect targeted and untargeted mutagenesis...
  58. ncbi DNA polymerase lambda from calf thymus preferentially replicates damaged DNA
    Kristijan Ramadan
    Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich Irchel, Winterthurerstrasse 190, CH 8057, Zurich, Switzerland
    J Biol Chem 277:18454-8. 2002
    ..homogeneity and identified as a 67-kDa polypeptide that cross-reacted with monoclonal antibodies against DNA polymerase beta and polyclonal antibodies against DNA polymerase lambda...
  59. pmc Base excision repair in early zebrafish development: evidence for DNA polymerase switching and standby AP endonuclease activity
    Sean Fortier
    Department of Biology, Northeastern University, Boston, Massachusetts 02115, USA
    Biochemistry 48:5396-404. 2009
    ..The switch to normal, adult BER occurs fully when the embryos hatch from the chorionic membrane and encounter normal oxidative stress...
  60. ncbi Investigating the role of the little finger domain of Y-family DNA polymerases in low fidelity synthesis and translesion replication
    Francois Boudsocq
    Section on DNA Replication, Repair, and Mutagenesis, Laboratory of Genomic Integrity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 2725, USA
    J Biol Chem 279:32932-40. 2004
    ..Our studies indicate that the unique but variable LF domain of Y-family polymerases plays a major role in determining the enzymatic and biological properties of each individual Y-family member...
  61. pmc A survey of splice variants of the human hypoxanthine phosphoribosyl transferase and DNA polymerase beta genes: products of alternative or aberrant splicing?
    Adonis Skandalis
    Department of Biology, Brock University, St Catharines, Ontario L2S 3A1, Canada
    Nucleic Acids Res 32:6557-64. 2004
    ..and quantified the aberrant splice variants in the human hypoxanthine phosphoribosyl transferase (HPRT) and DNA polymerase beta (POLB) in the presence and the absence of the Nonsense Mediated Decay (NMD) pathway, which removes ..
  62. pmc Yeast Tdp1 regulates the fidelity of nonhomologous end joining
    Karim Bahmed
    Molecular Pharmacology Department, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Proc Natl Acad Sci U S A 107:4057-62. 2010
    ....
  63. pmc Distinct energetics and closing pathways for DNA polymerase beta with 8-oxoG template and different incoming nucleotides
    Yanli Wang
    Department of Chemistry and Courant Institute of Mathematical Sciences, New York University, 251 Mercer Street, New York, NY 10012, USA
    BMC Struct Biol 7:7. 2007
    ..8-oxoG) is a common oxidative lesion frequently encountered by DNA polymerases such as the repair enzyme DNA polymerase beta (pol beta)...
  64. doi Structural insights into the generation of single-base deletions by the Y family DNA polymerase dbh
    Ryan C Wilson
    Division of Molecular Medicine, Wadsworth Center, New York State Department of Health, The State University of New York at Albany, Albany, NY 12201 0509, USA
    Mol Cell 29:767-79. 2008
    ....
  65. pmc NEIL2-initiated, APE-independent repair of oxidized bases in DNA: Evidence for a repair complex in human cells
    Aditi Das
    Department of Biochemistry and Molecular Biology, Sealy Center for Molecular Science, University of Texas Medical Branch, 6 136 Medical Research Building, Route 1079, Galveston, TX 77555, USA
    DNA Repair (Amst) 5:1439-48. 2006
    ..We have also observed stable interaction between NEIL2 and other BER proteins DNA polymerase beta (Pol beta), DNA ligase IIIalpha (Lig IIIalpha) and XRCC1...
  66. pmc Association of DNA polymerase mu (pol mu) with Ku and ligase IV: role for pol mu in end-joining double-strand break repair
    Kiran N Mahajan
    Lineberger Comprehensive Cancer Center, Mason Farm Road, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7295, USA
    Mol Cell Biol 22:5194-202. 2002
    ..In contrast, the related mammalian DNA polymerase beta does not form a complex with Ku and XRCC4-ligase IV and is less effective than pol mu in facilitating ..
  67. pmc Human methyl purine DNA glycosylase and DNA polymerase beta expression collectively predict sensitivity to temozolomide
    Ram N Trivedi
    Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213 1863, USA
    Mol Pharmacol 74:505-16. 2008
    ..In the present study, we show that both elevated MPG expression and short hairpin RNA-mediated loss of DNA polymerase beta (Pol beta) expression in human breast cancer cells increases cellular sensitivity to temozolomide...
  68. ncbi Efficient processing of DNA ends during yeast nonhomologous end joining. Evidence for a DNA polymerase beta (Pol4)-dependent pathway
    T E Wilson
    Department of Pathology, Division of Laboratory Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 274:23599-609. 1999
    ..We transformed yeast with a series of linearized plasmids to examine the role of Pol4 (Pol IV, DNA polymerase beta) in repair at a variety of end configurations...
  69. ncbi CHIP-mediated degradation and DNA damage-dependent stabilization regulate base excision repair proteins
    Jason L Parsons
    Medical Research Council Radiation Oncology and Biology Unit, University of Oxford, Oxfordshire OX1 3QU, UK
    Mol Cell 29:477-87. 2008
    ..The scaffold protein XRCC1, DNA polymerase beta, and DNA ligase IIIalpha play pivotal roles in BER...
  70. ncbi The dinB gene encodes a novel E. coli DNA polymerase, DNA pol IV, involved in mutagenesis
    J Wagner
    Division of Genetics and Mutagenesis, National Institute of Health Sciences, Tokyo, Japan
    Mol Cell 4:281-6. 1999
    ..Along with the sequence homologies previously found within the UmuC-like protein family, these results indicate that the uncovered DNA polymerase activity may be a common feature of all these homologous proteins...
  71. ncbi Implication of p53 in base excision DNA repair: in vivo evidence
    Young R Seo
    Indiana University Cancer Center, Department of Microbiology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    Oncogene 21:731-7. 2002
    ..One contributing factor is the abundance of DNA polymerase beta (beta-pol), an enzyme required for BER, which was almost absent in p53 mutant and p53-null cells...
  72. pmc Template strand scrunching during DNA gap repair synthesis by human polymerase lambda
    Miguel Garcia-Diaz
    Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, North Carolina, USA
    Nat Struct Mol Biol 16:967-72. 2009
    ..Thus, akin to scrunching by RNA polymerase during transcription initiation, scrunching occurs during gap filling DNA synthesis associated with DNA repair...
  73. pmc An SNF2 protein associated with nuclear RNA silencing and the spread of a silencing signal between cells in Arabidopsis
    Lisa M Smith
    Sainsbury Laboratory, John Ines Centre, Norwich NR4 7UH, United Kingdom
    Plant Cell 19:1507-21. 2007
    ..We interpret the effect of polymerase IVa and trans-acting siRNA pathway mutations in terms of a modular property of RNA silencing pathways...
  74. ncbi Crystal structure of a Y-family DNA polymerase in action: a mechanism for error-prone and lesion-bypass replication
    H Ling
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Cell 107:91-102. 2001
    ..Dpo4 is also captured in the crystal translocating two template bases to the active site at once, suggesting a possible mechanism for bypassing thymine dimers...
  75. pmc All three SOS-inducible DNA polymerases (Pol II, Pol IV and Pol V) are involved in induced mutagenesis
    R Napolitano
    UPR 9003, CNRS Cancerogenese et Mutagenese Moleculaire et Structurale, ESBS and IRCAD, Strasbourg, France
    EMBO J 19:6259-65. 2000
    ..Therefore, in response to the vast diversity of existing DNA damage, the cell uses a pool of 'translesional' DNA polymerases in order to bypass the various DNA lesions...
  76. ncbi Affinity capture of a mammalian DNA polymerase beta by inhibitors immobilized to resins used in solid-phase organic synthesis
    Kouji Kuramochi
    Genome and Drug Research Center, Tokyo University of Science, Noda, Chiba 278 8510, Japan
    Bioconjug Chem 16:97-104. 2005
    ..application of resins normally used in solid-phase organic synthesis to the affinity capture of a mammalian DNA polymerase beta (pol beta) is reported...
  77. pmc DNA polymerase beta overexpression stimulates the Rad51-dependent homologous recombination in mammalian cells
    Yvan Canitrot
    Genetic Instability and Cancer Group, Institut de Pharmacologie et de Biologie Structurale UMR CNRS 5089, 205 route de Narbonne, 31077 Toulouse, France
    Nucleic Acids Res 32:5104-12. 2004
    Overexpression of DNA polymerase beta (polbeta), an error-prone DNA repair enzyme, has been shown to result in mutagenesis, aneuploidy and tumorigenesis...
  78. ncbi Poly(ADP-ribose) polymerase-1 (PARP-1) is required in murine cell lines for base excision repair of oxidative DNA damage in the absence of DNA polymerase beta
    Florence Le Page
    Commissariat a l Energie Atomique CEA, Direction des Sciences du Vivant, Departement de Radiobiologie et Radiopathologie, Unité Mixte de Recherche 217 CNRS CEA Radiobiologie Moléculaire et Cellulaire, 92265 Fontenay aux Roses, France
    J Biol Chem 278:18471-7. 2003
    ....
  79. ncbi The role of base excision repair in the sensitivity and resistance to temozolomide-mediated cell death
    Ram N Trivedi
    Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213 1863, USA
    Cancer Res 65:6394-400. 2005
    ..Thus, the BER pathway is a major contributor to cellular resistance to temozolomide and its efficacy depends on specific BER gene expression and activity...
  80. pmc Alpha,beta-difluoromethylene deoxynucleoside 5'-triphosphates: a convenient synthesis of useful probes for DNA polymerase beta structure and function
    Thomas G Upton
    Department of Chemistry, University of Southern California, Los Angeles, California 90089, USA
    Org Lett 11:1883-6. 2009
    ....
  81. ncbi Structure/function analysis of the interaction of adenomatous polyposis coli with DNA polymerase beta and its implications for base excision repair
    Ramesh Balusu
    Department of Anatomy and Cell Biology, UF Shands Cancer Center, University of Florida, Gainesville, Florida 32610, USA
    Biochemistry 46:13961-74. 2007
    ..We have shown that APC interacts with DNA polymerase beta (Pol-beta) and flap endonuclease 1 (Fen-1) and blocks Pol-beta-directed strand-displacement synthesis...
  82. pmc An AP endonuclease 1-DNA polymerase beta complex: theoretical prediction of interacting surfaces
    Alexej Abyzov
    Department of Biology, Northeastern University, Boston, Massachusetts, United States of America
    PLoS Comput Biol 4:e1000066. 2008
    ..followed by nucleotide insertion and removal of the downstream deoxyribose moiety, performed most often by DNA polymerase beta (pol-beta)...
  83. pmc Parp1 activation in mouse embryonic fibroblasts promotes Pol beta-dependent cellular hypersensitivity to alkylation damage
    Elena Jelezcova
    Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, PA 15213, USA
    Mutat Res 686:57-67. 2010
    ..b>DNA polymerase beta (Pol beta) knockout (KO) MEFs are hypersensitive to the cytotoxic effect of alkylating agents, as compared ..
  84. ncbi Tumor suppressor APC blocks DNA polymerase beta-dependent strand displacement synthesis during long patch but not short patch base excision repair and increases sensitivity to methylmethane sulfonate
    Satya Narayan
    Department of Anatomy and Cell Biology and Shands Cancer Center, University of Florida, Gainesville, Florida 32610, USA
    J Biol Chem 280:6942-9. 2005
    ..We identified a proliferating cell nuclear antigen-interacting protein-like box sequence in APC that binds DNA polymerase beta and blocks DNA polymerase beta-mediated strand-displacement synthesis in long patch BER without affecting ..
  85. pmc UmuD(2) inhibits a non-covalent step during DinB-mediated template slippage on homopolymeric nucleotide runs
    James J Foti
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Biol Chem 285:23086-95. 2010
    ..UmuD(2), when bound to DinB, displaces the equilibrium in favor of the non-slipped conformation, thereby preventing frameshifting and potentially enhancing DinB activity on non-slipped substrates...
  86. pmc A novel inhibitor of DNA polymerase beta enhances the ability of temozolomide to impair the growth of colon cancer cells
    Aruna S Jaiswal
    Department of Anatomy and Cell Biology and University of Florida Shands Cancer Center, University of Florida, Gainesville, FL 32610, USA
    Mol Cancer Res 7:1973-83. 2009
    ..In the present study, we used structure-based molecular docking of DNA polymerase beta (Pol-beta) and identified a potent small molecular weight inhibitor, NSC-666715...
  87. doi Consecutive incorporation of fluorophore-labeled nucleotides by mammalian DNA polymerase beta
    Ken Hirano
    Nano Bioanalysis Team, Health Technology Research Center, National Institute of Advanced Industrial Science and Technology, Takamatsu, Kagawa 761 0395, Japan
    Anal Biochem 405:160-7. 2010
    ..We found that rat DNA polymerase beta (pol beta) consecutively incorporated fluorophore-labeled nucleotides to a greater extent than four ..
  88. pmc Efficient and accurate bypass of N2-(1-carboxyethyl)-2'-deoxyguanosine by DinB DNA polymerase in vitro and in vivo
    Bifeng Yuan
    Department of Chemistry and Environmental Toxicology Graduate Program, University of California, Riverside, CA 92521 0403, USA
    Proc Natl Acad Sci U S A 105:8679-84. 2008
    ..e., polymerase kappa), opposite the N(2)-CEdG is both accurate and efficient. Taken together, our data support that N(2)-CEdG, a minor-groove DNA adduct arising from MG, is an important endogenous substrate for DinB DNA polymerase...
  89. ncbi DNA adduct bypass polymerization by Sulfolobus solfataricus DNA polymerase Dpo4: analysis and crystal structures of multiple base pair substitution and frameshift products with the adduct 1,N2-ethenoguanine
    Hong Zang
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    J Biol Chem 280:29750-64. 2005
    ..We concluded that Dpo4 uses several mechanisms, including A incorporation opposite 1,N(2)-epsilon-G and also a variation of dNTP-stabilized misalignment, to generate both base pair and frameshift mutations...
  90. ncbi Hinge residue Ile260 of DNA polymerase beta is important for enzyme activity and fidelity
    Daniela Starcevic
    Program in Microbiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Biochemistry 44:3775-84. 2005
    ..They have evolved mechanisms for discriminating among very similar dNTP substrates. DNA polymerase beta is a repair polymerase that provides a model system for a direct study of insertion fidelity...
  91. ncbi Poly(ADP-ribose) polymerase-1 protects excessive DNA strand breaks from deterioration during repair in human cell extracts
    Jason L Parsons
    MRC Radiation and Genome Stability Unit, Harwell, Oxfordshire, UK
    FEBS J 272:2012-21. 2005
    ..Our data support the model in which PARP-1 binding to DNA single-strand breaks or repair intermediates plays a protective role when repair is limited...
  92. ncbi Solution structure of the lyase domain of human DNA polymerase lambda
    Eugene F Derose
    Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Box 12233, Research Triangle Park, North Carolina 27709, USA
    Biochemistry 42:9564-74. 2003
    ..g., K60 in pol beta and K307 in pol lambda. Additionally, on the basis of the structural alignment obtained, several previously proposed mechanistic hypotheses can be evaluated...
  93. pmc Neonatal lethality with abnormal neurogenesis in mice deficient in DNA polymerase beta
    N Sugo
    Kihara Institute for Biological Research, Graduate School of Integrated Science, Yokohama City University, Totsuka ku, Yokohama 244 0813, USA
    EMBO J 19:1397-404. 2000
    b>DNA polymerase beta (Polbeta) has been implicated in base excision repair in mammalian cells. However, the physiological significance of this enzyme in the body remains unclear...
  94. ncbi DNA polymerase beta interacts with TRF2 and induces telomere dysfunction in a murine mammary cell line
    Poppy Fotiadou
    Departments of Therapeutic Radiology and Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Cancer Res 64:3830-7. 2004
    b>DNA polymerase beta (Polbeta) is a DNA repair protein that functions in base excision repair and meiosis. The enzyme has deoxyribose phosphate lyase and polymerase activity, but it is error prone because it bears no proofreading activity...
  95. ncbi Kinetic mechanisms of rat polymerase beta-ssDNA interactions. Quantitative fluorescence stopped-flow analysis of the formation of the (Pol beta)(16) and (Pol beta)(5) ssDNA binding mode
    M J Jezewska
    Department of Human Biological Chemistry and Genetics and the Sealy Center for Structural Biology, The University of Texas Medical Branch at Galveston, Galveston, TX 77555 1053, USA
    J Mol Biol 313:977-1002. 2001
    ..The sequential nature of the determined mechanisms indicates a lack of kinetically significant conformational equilibrium of rat pol beta, prior to ssDNA binding...
  96. ncbi DNA elongation by the human DNA polymerase lambda polymerase and terminal transferase activities are differentially coordinated by proliferating cell nuclear antigen and replication protein A
    Giovanni Maga
    Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, via Abbiategrasso 207, I 27100 Pavia, Italy
    J Biol Chem 280:1971-81. 2005
    ....
  97. ncbi DNA polymerase lambda mediates a back-up base excision repair activity in extracts of mouse embryonic fibroblasts
    Elena K Braithwaite
    Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 280:18469-75. 2005
    ..In addition, the pol lambda antibody strongly reduced in vitro BER in the pol beta -/- cell extract. These data indicate that pol lambda is able to contribute to BER in mouse fibroblast cell extract...
  98. ncbi Identification of small molecule synthetic inhibitors of DNA polymerase beta by NMR chemical shift mapping
    Hong Yu Hu
    Department of Biochemistry, University of Connecticut Health Center, Farmington, Connecticut 06032, USA
    J Biol Chem 279:39736-44. 2004
    b>DNA polymerase beta (beta-pol) plays a central role in repair of damaged DNA bases by base excision repair (BER) pathways...
  99. ncbi Is there a link between DNA polymerase beta and cancer?
    Daniela Starcevic
    Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Cell Cycle 3:998-1001. 2004
    Recent small-scale studies have shown that 30% of human tumors examined to date express DNA polymerase beta variant proteins...
  100. pmc The accumulation of MMS-induced single strand breaks in G1 phase is recombinogenic in DNA polymerase beta defective mammalian cells
    Barbara Pascucci
    Istituto di Cristallografia, CNR, Sezione di Roma PO Box 10, 00016 Monterotondo Stazione, Roma, Italy
    Nucleic Acids Res 33:280-8. 2005
    ..This is an example of a coordinated effort of two different repair pathways, BER and HR, to protect mammalian cells from alkylation-induced cytotoxicity...
  101. ncbi Distinct beta-clamp interactions govern the activities of the Y family PolIV DNA polymerase
    Jérôme Wagner
    CNRS FRE3211, ESBS, Universite de Strasbourg, BP 10413, 67412 Strasbourg Cedex, France
    Mol Microbiol 74:1143-51. 2009
    ..This discloses two independent modes of action for PolIV and, in turn, uncovers a novel way by which the cell may regulate the potentially deleterious effect of such low fidelity polymerases during replication...

Research Grants72

  1. MECHANISM OF BASE EXCISION REPAIR IN HIGHER EUKARYOTES
    Yoshihiro Matsumoto; Fiscal Year: 2003
    ..The first specific aim is to elucidate the excision mechanism of a 5'- incised AP site by DNA polymerase beta (pol beta) from structural and functional perspectives...
  2. RNA-Mediated Silencing: Mechanisms and Biological Roles in Chlamydomonas
    Heriberto Cerutti; Fiscal Year: 2007
    ..One group encodes factors that appear to be directly involved in RNAi: Mut68p, a putative DNA polymerase beta-like nucleotidyltransferase; MutTOp, a homolog of the vasa intronic gene product; and Mut91p, a novel but ..
  3. HYDROXYL RADICAL BIOLOGY BY CEREBRAL ISCHEMIA
    Philip Liu; Fiscal Year: 1999
    ..This model will be suitable for exploring pathobiological effect of oxygen stress, and for testing drugs that reduce or abolish the damaging effect of hydroxyl radical after stroke. ..
  4. HYDROXYL RADICAL BIOLOGY BY CEREBRAL ISCHEMIA
    Philip Liu; Fiscal Year: 1999
    ..This model will be suitable for exploring pathobiological effect of oxygen stress, and for testing drugs that reduce or abolish the damaging effect of hydroxyl radical after stroke. ..
  5. BIOPHYSICAL AND SCANNING FORCE MICROSCOPY STUDIES
    DOROTHY ERIE; Fiscal Year: 2001
    ..b>DNA polymerase beta subsequently extends the DNA chain by one nucleotide and removes the dRP site with its dRP lyase activity, ..
  6. RNA-Mediated Silencing: Mechanisms and Biological Roles in Chlamydomonas
    Heriberto Cerutti; Fiscal Year: 2006
    ..One group encodes factors that appear to be directly involved in RNAi: Mut68p, a putative DNA polymerase beta-like nucleotidyltransferase; MutTOp, a homolog of the vasa intronic gene product; and Mut91p, a novel but ..
  7. RNA-Mediated Silencing: Mechanisms and Biological Roles in Chlamydomonas
    Heriberto Cerutti; Fiscal Year: 2009
    ..One group encodes factors that appear to be directly involved in RNAi: Mut68p, a putative DNA polymerase beta-like nucleotidyltransferase;MutTOp, a homolog of the vasa intronic gene product;and Mut91p, a novel but ..
  8. BIOPHYSICAL AND SCANNING FORCE MICROSCOPY STUDIES
    DOROTHY ERIE; Fiscal Year: 1999
    ..b>DNA polymerase beta subsequently extends the DNA chain by one nucleotide and removes the dRP site with its dRP lyase activity, ..
  9. HUMAN DNA REPAIR ENZYMES FOR REDOX AND ALKYLATION DAMAGE
    Bruce Demple; Fiscal Year: 2000
    ..The interaction of the Ape protein with DNA polymerase beta and other proteins (detected by the yeast two-hybrid system or phage display) will be characterized.
  10. BIOPHYSICAL AND SCANNING FORCE MICROSCOPY STUDIES
    DOROTHY ERIE; Fiscal Year: 2000
    ..b>DNA polymerase beta subsequently extends the DNA chain by one nucleotide and removes the dRP site with its dRP lyase activity, ..
  11. HUMAN DNA REPAIR ENZYMES FOR REDOX AND ALKYLATION DAMAGE
    Bruce Demple; Fiscal Year: 1999
    ..The interaction of the Ape protein with DNA polymerase beta and other proteins (detected by the yeast two-hybrid system or phage display) will be characterized.
  12. FUNCTION OF PCNA IN CELLULAR DNA REPAIR
    Yoshihiro Matsumoto; Fiscal Year: 2000
    ..In the past, base excision repair was thought to proceed exclusively by a DNA polymerase beta (pol beta)-dependent pathway...
  13. ROLES OF DNA LIGASE I IN MAMMALIAN DNA METABOLISM
    Alan Tomkinson; Fiscal Year: 2000
    ..Sam Wilson, we have identified an interaction between DNA ligase I and DNA polymerase beta within a multiprotein base excision repair complex...
  14. ROLES OF DNA LIGASE I IN MAMMALIAN DNA METABOLISM
    Alan Tomkinson; Fiscal Year: 2005
    ..Sam Wilson, we have identified an interaction between DNA ligase I and DNA polymerase beta within a multiprotein base excision repair complex...
  15. ROLES OF DNA LIGASE I IN MAMMALIAN DNA METABOLISM
    Alan Tomkinson; Fiscal Year: 2003
    ..Sam Wilson, we have identified an interaction between DNA ligase I and DNA polymerase beta within a multiprotein base excision repair complex...
  16. ROLES OF DNA LIGASE I IN MAMMALIAN DNA METABOLISM
    Alan Tomkinson; Fiscal Year: 2002
    ..Sam Wilson, we have identified an interaction between DNA ligase I and DNA polymerase beta within a multiprotein base excision repair complex...
  17. FUNCTION OF PCNA IN CELLULAR DNA REPAIR
    Yoshihiro Matsumoto; Fiscal Year: 2001
    ..In the past, base excision repair was thought to proceed exclusively by a DNA polymerase beta (pol beta)-dependent pathway...
  18. FUNCTION OF PCNA IN CELLULAR DNA REPAIR
    Yoshihiro Matsumoto; Fiscal Year: 1999
    ..In the past, base excision repair was thought to proceed exclusively by a DNA polymerase beta (pol beta)-dependent pathway...
  19. ROLES OF DNA LIGASE I IN MAMMALIAN DNA METABOLISM
    Alan Tomkinson; Fiscal Year: 2001
    ..Sam Wilson, we have identified an interaction between DNA ligase I and DNA polymerase beta within a multiprotein base excision repair complex...
  20. ROLES OF DNA LIGASE I IN MAMMALIAN DNA METABOLISM
    Alan Tomkinson; Fiscal Year: 2003
    ..Sam Wilson, we have identified an interaction between DNA ligase I and DNA polymerase beta within a multiprotein base excision repair complex...
  21. HUMAN DNA REPAIR ENZYMES FOR REDOX AND ALKYLATION DAMAGE
    BRUCE F DEMPLE; Fiscal Year: 2009
    ..generate abasic sites, which are further processed in several steps dependent on the Ape1 endonuclease and DNA polymerase beta. Our long-term goal has been to ascertain the biological functions of Ape1 protein as a central player in ..
  22. HUMAN DNA REPAIR ENZYMES FOR REDOX AND ALKYLATION DAMAGE
    BRUCE F DEMPLE; Fiscal Year: 2010
    ..generate abasic sites, which are further processed in several steps dependent on the Ape1 endonuclease and DNA polymerase beta. Our long-term goal has been to ascertain the biological functions of Ape1 protein as a central player in ..
  23. HUMAN DNA REPAIR ENZYMES FOR REDOX AND ALKYLATION DAMAGE
    Bruce Demple; Fiscal Year: 2007
    ..generate abasic sites, which are further processed in several steps dependent on the Ape1 endonuclease and DNA polymerase beta. Our long-term goal has been to ascertain the biological functions of Ape1 protein as a central player in ..
  24. HUMAN DNA REPAIR ENZYMES FOR REDOX AND ALKYLATION DAMAGE
    Bruce Demple; Fiscal Year: 2009
    ..generate abasic sites, which are further processed in several steps dependent on the Ape1 endonuclease and DNA polymerase beta. Our long-term goal has been to ascertain the biological functions of Ape1 protein as a central player in ..
  25. MUTATIONAL MECHANISMS OF REPETITIVE DNA IN HUMAN CELLS
    Kristin Eckert; Fiscal Year: 2001
    ..These targets will be used as DNA templates during in vitro DNA synthesis catalyzed by human DNA polymerase beta and the calf thymus polymerase alpha-primase complex...
  26. MUTATIONAL MECHANISMS OF REPETITIVE DNA IN HUMAN CELLS
    Kristin Eckert; Fiscal Year: 2000
    ..These targets will be used as DNA templates during in vitro DNA synthesis catalyzed by human DNA polymerase beta and the calf thymus polymerase alpha-primase complex...
  27. MUTATIONAL MECHANISMS OF REPETITIVE DNA IN HUMAN CELLS
    Kristin Eckert; Fiscal Year: 1999
    ..These targets will be used as DNA templates during in vitro DNA synthesis catalyzed by human DNA polymerase beta and the calf thymus polymerase alpha-primase complex...
  28. MECHANISM OF BASE EXCISION REPAIR IN HIGHER EUKARYOTES
    Yoshihiro Matsumoto; Fiscal Year: 2001
    ..The first specific aim is to elucidate the excision mechanism of a 5'- incised AP site by DNA polymerase beta (pol beta) from structural and functional perspectives...
  29. Base excision repair in zebrafish development
    PHYLLIS STRAUSS; Fiscal Year: 2007
    ..These studies will help define the role of BER in embryogenesis and open a new field of inquiry. [unreadable] [unreadable] [unreadable]..
  30. Base excision repair in zebrafish development
    PHYLLIS STRAUSS; Fiscal Year: 2006
    ..These studies will help define the role of BER in embryogenesis and open a new field of inquiry. [unreadable] [unreadable] [unreadable]..
  31. MECHANISM OF BASE EXCISION REPAIR IN HIGHER EUKARYOTES
    Yoshihiro Matsumoto; Fiscal Year: 2002
    ..The first specific aim is to elucidate the excision mechanism of a 5'- incised AP site by DNA polymerase beta (pol beta) from structural and functional perspectives...
  32. MECHANISM OF BASE EXCISION REPAIR IN HIGHER EUKARYOTES
    Yoshihiro Matsumoto; Fiscal Year: 1999
    ..The first specific aim is to elucidate the excision mechanism of a 5'- incised AP site by DNA polymerase beta (pol beta) from structural and functional perspectives...
  33. MECHANISM OF BASE EXCISION REPAIR IN HIGHER EUKARYOTES
    Yoshihiro Matsumoto; Fiscal Year: 2000
    ..The first specific aim is to elucidate the excision mechanism of a 5'- incised AP site by DNA polymerase beta (pol beta) from structural and functional perspectives...
  34. MECHANISMS OF FIDELITY AND MUTAGENESIS
    Thomas Spratt; Fiscal Year: 2004
    ..Two polymerases will be studied, DNA polymerase I of E. coli and mammalian DNA polymerase beta. The biochemical mechanisms of DNA synthesis by these proteins have been well studied, thus providing a ..
  35. MECHANISMS OF FIDELITY AND MUTAGENESIS
    Thomas Spratt; Fiscal Year: 2002
    ..Two polymerases will be studied, DNA polymerase I of E. coli and mammalian DNA polymerase beta. The biochemical mechanisms of DNA synthesis by these proteins have been well studied, thus providing a ..
  36. MECHANISMS OF FIDELITY AND MUTAGENESIS
    Thomas Spratt; Fiscal Year: 2005
    ..Two polymerases will be studied, DNA polymerase I of E. coli and mammalian DNA polymerase beta. The biochemical mechanisms of DNA synthesis by these proteins have been well studied, thus providing a ..
  37. MECHANISMS OF FIDELITY AND MUTAGENESIS
    Thomas Spratt; Fiscal Year: 2004
    ..Two polymerases will be studied, DNA polymerase I of E. coli and mammalian DNA polymerase beta. The biochemical mechanisms of DNA synthesis by these proteins have been well studied, thus providing a ..
  38. MECHANISMS OF FIDELITY AND MUTAGENESIS
    Thomas Spratt; Fiscal Year: 2003
    ..Two polymerases will be studied, DNA polymerase I of E. coli and mammalian DNA polymerase beta. The biochemical mechanisms of DNA synthesis by these proteins have been well studied, thus providing a ..
  39. DNA POLYMERASES IN NORMAL AND CANCER CELLS
    LUCY CHANG; Fiscal Year: 1990
    ..4. To compare the structure of DNA polymerases and DNA primase in normal and transformed cells at protein, RNA and genomic levels...
  40. ENZYMOLOGY/BIOLOGY OF HUMAN G:T DNA BASE MISMATCH REPAIR
    RUFUS DAY; Fiscal Year: 1993
    ..gap produced by mismatch removal of T across from template m6G, and evaluate the possibility that the DNA polymerase beta of A12356-MR4 is altered...
  41. NUCLEAR TARGETS FOR NATURAL PRODUCTS DRUG DISCOVERY
    SIDNEY HECHT; Fiscal Year: 1999
    ..3) obtaining more potent inhibitors of DNA polymerase beta so that it is possible to complete the testing of the hypothesis that these agents can potentiate the ..
  42. Folate Deficiency and Susceptibility to GI Disease
    AHMAD HEYDARI; Fiscal Year: 2003
    ..The model of BER deficiency used in these studies is the DNA polymerase Beta heterozygous knockout mouse...
  43. Folate Deficiency and Susceptibility to GI Disease
    AHMAD HEYDARI; Fiscal Year: 2002
    ..The model of BER deficiency used in these studies is the DNA polymerase Beta heterozygous knockout mouse...
  44. NUCLEAR TARGETS FOR NATURAL PRODUCTS DRUG DISCOVERY
    SIDNEY HECHT; Fiscal Year: 1999
    ..3) obtaining more potent inhibitors of DNA polymerase beta so that it is possible to complete the testing of the hypothesis that these agents can potentiate the ..
  45. NUCLEAR TARGETS FOR NATURAL PRODUCTS DRUG DISCOVERY
    SIDNEY HECHT; Fiscal Year: 2000
    ..3) obtaining more potent inhibitors of DNA polymerase beta so that it is possible to complete the testing of the hypothesis that these agents can potentiate the ..
  46. The Effect of Mre11/Rad50on Fidelity of Synthesis by DNA Polymerase Beta
    Drew Murphy; Fiscal Year: 2007
    ..b>DNA polymerase Beta (pol-beta) is the main polymerase involved in base excision repair (BER), which is a major mechanism of ..
  47. AN ENVIRONMENTALLY RELEVANT DNA POL BETA VARIANT
    Sipra Banerjee; Fiscal Year: 2003
    For the elucidation of functionally important DNA polymerase beta (polbeta) variant, we propose experiments to test a hypothesis of whether a defective repair gene, such as polbeta, has a contributory role in the increased disease risks ..
  48. AN ENVIRONMENTALLY RELEVANT DNA POL BETA VARIANT
    Sipra Banerjee; Fiscal Year: 2000
    For the elucidation of functionally important DNA polymerase beta (polbeta) variant, we propose experiments to test a hypothesis of whether a defective repair gene, such as polbeta, has a contributory role in the increased disease risks ..
  49. Transcription coupled repair of oxidative DNA damage
    BRETT HALTIWANGER; Fiscal Year: 2003
    ..And (2) that transcription-coupled BER of oxidative damage which requires XPG proceeds by a DNA polymerase beta independent pathway, with the possible involvement of XPG in the selection of the repair patch pathway...
  50. AN ENVIRONMENTALLY RELEVANT DNA POL BETA VARIANT
    Sipra Banerjee; Fiscal Year: 2002
    For the elucidation of functionally important DNA polymerase beta (polbeta) variant, we propose experiments to test a hypothesis of whether a defective repair gene, such as polbeta, has a contributory role in the increased disease risks ..
  51. AN ENVIRONMENTALLY RELEVANT DNA POL BETA VARIANT
    Sipra Banerjee; Fiscal Year: 2001
    For the elucidation of functionally important DNA polymerase beta (polbeta) variant, we propose experiments to test a hypothesis of whether a defective repair gene, such as polbeta, has a contributory role in the increased disease risks ..
  52. CORE--DNA DAMAGE AND MUTAGENESIS
    LAWRENCE LEOB; Fiscal Year: 2002
    ..Together these studies on oxygen free radical damage and mutations provide a spectrum of probes to analyze the contribution of oxygen free radical damage to these important cancers. ..
  53. CORE--DNA DAMAGE AND MUTAGENESIS
    LAWRENCE LEOB; Fiscal Year: 2000
    ..Together these studies on oxygen free radical damage and mutations provide a spectrum of probes to analyze the contribution of oxygen free radical damage to these important cancers. ..
  54. CORE--DNA DAMAGE AND MUTAGENESIS
    LAWRENCE LEOB; Fiscal Year: 2001
    ..Together these studies on oxygen free radical damage and mutations provide a spectrum of probes to analyze the contribution of oxygen free radical damage to these important cancers. ..
  55. CORE--DNA DAMAGE AND MUTAGENESIS
    LAWRENCE LEOB; Fiscal Year: 1999
    ..Together these studies on oxygen free radical damage and mutations provide a spectrum of probes to analyze the contribution of oxygen free radical damage to these important cancers. ..
  56. Base Excision Repair, Genetic Integrity & Health Span
    CHRISTI WALTER; Fiscal Year: 2004
    ..The overall hypothesis to be tested is that modulation of DNA polymerase beta abundance/activity will have differential effects among tissues relative to age...
  57. Base Excision Repair, Genetic Integrity & Health Span
    CHRISTI WALTER; Fiscal Year: 2006
    ..The overall hypothesis to be tested is that modulation of DNA polymerase beta abundance/activity will have differential effects among tissues relative to age...
  58. Base Excision Repair, Genetic Integrity & Health Span
    CHRISTI WALTER; Fiscal Year: 2005
    ..The overall hypothesis to be tested is that modulation of DNA polymerase beta abundance/activity will have differential effects among tissues relative to age...
  59. Base Excision Repair, Genetic Integrity & Health Span
    CHRISTI WALTER; Fiscal Year: 2007
    ..The overall hypothesis to be tested is that modulation of DNA polymerase beta abundance/activity will have differential effects among tissues relative to age...
  60. DOSE AND TIME FACTORS IN CELLULAR RADIOSENSITIVITY
    Joel Bedford; Fiscal Year: 1990
    ..to their location on human chromosomes in CHO/human hybrids and (8) isolate mutants deficient in (a) DNA Polymerase beta and (b) glutathione or glutathione transferase to assess the role of these in modulating cellular responses ..
  61. DNA POLYMERASE BETA AND CELLULAR TRANSFORMATION
    Joann Sweasy; Fiscal Year: 2002
    ..The results obtained from these studies have the potential to further our understanding of the molecular basis of cellular transformation and, therefore, neoplastic disease. ..
  62. DNA POLYMERASE BETA AND CELLULAR TRANSFORMATION
    Joann Sweasy; Fiscal Year: 2001
    ..The results obtained from these studies have the potential to further our understanding of the molecular basis of cellular transformation and, therefore, neoplastic disease. ..
  63. DNA POLYMERASE BETA AND CELLULAR TRANSFORMATION
    Joann Sweasy; Fiscal Year: 2000
    ..The results obtained from these studies have the potential to further our understanding of the molecular basis of cellular transformation and, therefore, neoplastic disease. ..
  64. DNA POLYMERASE BETA AND CELLULAR TRANSFORMATION
    Joann Sweasy; Fiscal Year: 1999
    ..The results obtained from these studies have the potential to further our understanding of the molecular basis of cellular transformation and, therefore, neoplastic disease. ..
  65. HUMAN XRCC1 PROTEIN IN DNA REPAIR AND RECOMBINATION
    MICHAEL THELEN; Fiscal Year: 2000
    ..XRCC1 protein was later shown to interact with several BER participants, namely DNA Ligase III, DNA Polymerase Beta, and Poly(ADP-Ribose) Polymerase...
  66. HUMAN XRCC1 PROTEIN IN DNA REPAIR AND RECOMBINATION
    MICHAEL THELEN; Fiscal Year: 1999
    ..XRCC1 protein was later shown to interact with several BER participants, namely DNA Ligase III, DNA Polymerase Beta, and Poly(ADP-Ribose) Polymerase...
  67. HUMAN XRCC1 PROTEIN IN DNA REPAIR AND RECOMBINATION
    MICHAEL THELEN; Fiscal Year: 1999
    ..XRCC1 protein was later shown to interact with several BER participants, namely DNA Ligase III, DNA Polymerase Beta, and Poly(ADP-Ribose) Polymerase...
  68. HUMAN XRCC1 PROTEIN IN DNA REPAIR AND RECOMBINATION
    MICHAEL THELEN; Fiscal Year: 2001
    ..XRCC1 protein was later shown to interact with several BER participants, namely DNA Ligase III, DNA Polymerase Beta, and Poly(ADP-Ribose) Polymerase...
  69. NMR STRUCTURAL OF DNA POLYMERASE B
    Mark Maciejewski; Fiscal Year: 2001
    Mammalian DNA polymerase beta catalyzes abasic site excision and nucleotidyl transfer in DNA repair and replication in mammalian cells. The enzyme is central to the repair of environmentally induced DNA damage in humans...
  70. NMR STRUCTURAL OF DNA POLYMERASE B
    Mark Maciejewski; Fiscal Year: 2003
    Mammalian DNA polymerase beta catalyzes abasic site excision and nucleotidyl transfer in DNA repair and replication in mammalian cells. The enzyme is central to the repair of environmentally induced DNA damage in humans...