Research Topics
Genomes and Genes
Species
| dna polymerase betaSummarySummary: A DNA repair enzyme that catalyzes DNA synthesis during base excision DNA repair. EC 2.7.7.7. Top Publications
Research Grants
| Scientific Experts
|
Detail Information
Publications
Structural insight into recruitment of translesion DNA polymerase Dpo4 to sliding clamp PCNAGuangxin Xing
Department of Biochemistry, University of Western Ontario, London, Ontario, Canada
Mol Microbiol 71:678-91. 2009....
Modulation of DNA polymerase beta-dependent base excision repair in cultured human cells after low dose exposure to arsenitePeter 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...
Mechanism of error-free and semitargeted mutagenic bypass of an aromatic amine lesion by Y-family polymerase Dpo4Olga 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...
Y-family DNA polymerases in Escherichia coliDaniel 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...
DNA polymerase beta and flap endonuclease 1 enzymatic specificities sustain DNA synthesis for long patch base excision repairYuan Liu
Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
J Biol Chem 280:3665-74. 2005b>DNA polymerase beta (pol beta) and flap endonuclease 1 (FEN1) are key players in pol beta-mediated long-patch base excision repair (LP-BER)...
UmuD and RecA directly modulate the mutagenic potential of the Y family DNA polymerase DinBVeronica 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...
Investigating the role of the little finger domain of Y-family DNA polymerases in low fidelity synthesis and translesion replicationFrancois 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...
Roles of chromosomal and episomal dinB genes encoding DNA pol IV in targeted and untargeted mutagenesis in Escherichia coliS 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...
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 ..
DNA polymerase lambda from calf thymus preferentially replicates damaged DNAKristijan Ramadan
Institute of Veterinary Biochemistry and Molecular Biology, , Winterthurerstrasse 190, CH-8057, , 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...
Base excision repair in early zebrafish development: evidence for DNA polymerase switching and standby AP endonuclease activitySean 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...
Yeast Tdp1 regulates the fidelity of nonhomologous end joiningKarim 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....
Efficient processing of DNA ends during yeast nonhomologous end joining. Evidence for a DNA polymerase beta (Pol4)-dependent pathwayT 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...
Structure/function analysis of the interaction of adenomatous polyposis coli with DNA polymerase beta and its implications for base excision repairRamesh 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...
The role of base excision repair in the sensitivity and resistance to temozolomide-mediated cell deathRam 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...
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 sulfonateSatya 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 ..
Affinity capture of a mammalian DNA polymerase beta by inhibitors immobilized to resins used in solid-phase organic synthesisKouji 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...
DNA polymerase beta overexpression stimulates the Rad51-dependent homologous recombination in mammalian cellsYvan 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. 2004Overexpression of DNA polymerase beta (polbeta), an error-prone DNA repair enzyme, has been shown to result in mutagenesis, aneuploidy and tumorigenesis...
A novel inhibitor of DNA polymerase beta enhances the ability of temozolomide to impair the growth of colon cancer cellsAruna 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...
Parp1 activation in mouse embryonic fibroblasts promotes Pol beta-dependent cellular hypersensitivity to alkylation damageElena 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 ..
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 betaFlorence 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....
Coordination between polymerase beta and FEN1 can modulate CAG repeat expansionYuan 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...
Alpha,beta-difluoromethylene deoxynucleoside 5'-triphosphates: a convenient synthesis of useful probes for DNA polymerase beta structure and functionThomas G Upton
Department of Chemistry, University of Southern California, Los Angeles, California 90089, USA
Org Lett 11:1883-6. 2009....
An AP endonuclease 1-DNA polymerase beta complex: theoretical prediction of interacting surfacesAlexej 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)...
UmuD(2) inhibits a non-covalent step during DinB-mediated template slippage on homopolymeric nucleotide runsJames 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...
DNA polymerase beta ribonucleotide discrimination: insertion, misinsertion, extension, and codingNisha 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...
Consecutive incorporation of fluorophore-labeled nucleotides by mammalian DNA polymerase betaKen 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 ..
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-ethenoguanineHong 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...
Efficient and accurate bypass of N2-(1-carboxyethyl)-2'-deoxyguanosine by DinB DNA polymerase in vitro and in vivoBifeng 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...
All three SOS-inducible DNA polymerases (Pol II, Pol IV and Pol V) are involved in induced mutagenesisR 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...
A DNA polymerase beta mutator mutant with reduced nucleotide discrimination and increased protein stabilityA M Shah
Department of Therapeutic Radiology and Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, USA
Biochemistry 40:11372-81. 2001b>DNA polymerase beta (pol beta) offers a simple system to examine the role of polymerase structure in the fidelity of DNA synthesis. In this study, the M282L variant of pol beta (M282Lbeta) was identified using an in vivo genetic screen...
DNA polymerase X of African swine fever virus: insertion fidelity on gapped DNA substrates and AP lyase activity support a role in base excision repair of viral DNARamón García-Escudero
Centro de Biología Molecular Severo Ochoa Consejo Superior de Investigaciones Científicas Universidad Autónoma de Madrid, Facultad de Ciencias, Universidad Autonoma de Madrid, Cantoblanco, 28049, Madrid, Spain
J Mol Biol 326:1403-12. 2003..Altogether, the results support a role for ASFV pol X in reparative BER of damaged viral DNA during ASFV infection...
Modifying the beta,gamma leaving-group bridging oxygen alters nucleotide incorporation efficiency, fidelity, and the catalytic mechanism of DNA polymerase betaChristopher A Sucato
Department of Chemistry, University of Southern California, Los Angeles, California 90089, USA
Biochemistry 46:461-71. 2007..The results are addressed theoretically in terms of the energetics of successive primer 3'-O addition (bond forming) and pyrophosphate analogue elimination (bond breaking) reaction energy barriers...
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 modeM 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...
DNA elongation by the human DNA polymerase lambda polymerase and terminal transferase activities are differentially coordinated by proliferating cell nuclear antigen and replication protein AGiovanni Maga
Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, via Abbiategrasso 207, I 27100 Pavia, Italy
J Biol Chem 280:1971-81. 2005....
Regulatory roles of p21 and apurinic/apyrimidinic endonuclease 1 in base excision repairS Tom
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
J Biol Chem 276:48781-9. 2001..Differential regulation by p21 is likely to relate to the utilization of DNA polymerase beta, which is not sensitive to p21, in the repair pathway...
Mechanism of adenomatous polyposis coli (APC)-mediated blockage of long-patch base excision repairAruna S Jaiswal
Department of Anatomy and Cell Biology and UF Shands Cancer Center, University of Florida, Gainesville, Florida 32610, USA
Biochemistry 45:15903-14. 2006Recently, we found an interaction between adenomatous polyposis coli (APC) and DNA polymerase beta (pol-beta) and showed that APC blocks strand-displacement synthesis of long-patch base excision repair (LP-BER) (Narayan, S., Jaiswal, A...
Polymerase mu is a DNA-directed DNA/RNA polymeraseStephanie A Nick McElhinny
Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
Mol Cell Biol 23:2309-15. 2003....
Misalignment-mediated DNA polymerase beta mutations: comparison of microsatellite and frame-shift error rates using a forward mutation assayKristin 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...
Solution structure of the lyase domain of human DNA polymerase lambdaEugene 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...
DNA polymerase beta interacts with TRF2 and induces telomere dysfunction in a murine mammary cell linePoppy Fotiadou
Departments of Therapeutic Radiology and Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
Cancer Res 64:3830-7. 2004b>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...
Deficiency in DNA polymerase beta provokes replication-dependent apoptosis via DNA breakage, Bcl-2 decline and caspase-3/9 activationKirsten Ochs
Division of Applied Toxicology, Institute of Toxicology, University of Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz, Germany
Cancer Res 62:1524-30. 2002Cells deficient in DNA polymerase beta (beta-pol) are impaired in base excision repair (BER) and hypersensitive to various DNA damaging agents, including methylating mutagens...
Hinge residue Ile260 of DNA polymerase beta is important for enzyme activity and fidelityDaniela 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...
Involvement of DNA polymerase beta in protection against the cytotoxicity of oxidative DNA damageJulie K Horton
Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, NC 27709, USA
DNA Repair (Amst) 1:317-33. 2002We had shown previously that DNA polymerase beta (beta-pol) null mouse fibroblasts, deficient in base excision repair (BER), are hypersensitive to monofunctional methylating agents but not to hydrogen peroxide (H2O2)...
Loss of DNA polymerase beta stacking interactions with templating purines, but not pyrimidines, alters catalytic efficiency and fidelityWilliam A Beard
Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
J Biol Chem 277:8235-42. 2002..Upon binding a correct deoxynucleoside triphosphate, alpha-helix N of DNA polymerase beta is observed to form one face of the binding pocket for the new base pair...
Energy analysis of chemistry for correct insertion by DNA polymerase betaPing Lin
Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599, USA
Proc Natl Acad Sci U S A 103:13294-9. 2006X-ray crystallographic structures of human DNA polymerase beta with nonhydrolyzable analogs containing all atoms in the active site required for catalysis provide a secure starting point for a theoretical analysis (quantum mechanics/..
Identification of small molecule synthetic inhibitors of DNA polymerase beta by NMR chemical shift mappingHong-Yu Hu
Department of Biochemistry, University of Connecticut Health Center, Farmington, Connecticut 06032, USA
J Biol Chem 279:39736-44. 2004b>DNA polymerase beta (beta-pol) plays a central role in repair of damaged DNA bases by base excision repair (BER) pathways...
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. 2004Recent small-scale studies have shown that 30% of human tumors examined to date express DNA polymerase beta variant proteins...
Translesional synthesis past acetylaminofluorene-derived DNA adducts catalyzed by human DNA polymerase kappa and Escherichia coli DNA polymerase IVN Suzuki
Laboratory of Chemical Biology, Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, New York 11794-8651, USA
Biochemistry 40:15176-83. 2001..et al. (2001) Biochemistry 40, 3717-3722], supporting a model in which pol kappa plays a role in translesion synthesis past acetylaminofluorene-derived lesions in mammalian cells...
Purification and characterization of pol kappa, a DNA polymerase encoded by the human DINB1 geneV L Gerlach
Laboratory of Molecular Pathology, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9072, USA
J Biol Chem 276:92-8. 2001....
The Leu22Pro tumor-associated variant of DNA polymerase beta is dRP lyase deficientShibani Dalal
Department of Therapeutic Radiology and Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, USA
Nucleic Acids Res 36:411-22. 2008Approximately 30% of human tumors characterized to date express DNA polymerase beta (pol beta) variant proteins...
Incorporation of non-nucleoside triphosphate analogues opposite to an abasic site by human DNA polymerases beta and lambdaEmmanuele Crespan
Istituto di Genetica Molecolare IGM-CNR via Abbiategrasso 207, I-27100 Pavia, Italy
Nucleic Acids Res 33:4117-27. 2005..These results show for the first time that neither the base nor the sugar moieties of nucleotides are required for incorporation by family X DNA polymerases...
Distinct beta-clamp interactions govern the activities of the Y family PolIV DNA polymeraseJérôme 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...
Simulating the effect of DNA polymerase mutations on transition-state energetics and fidelity: evaluating amino acid group contribution and allosteric coupling for ionized residues in human pol betaYun Xiang
Department of Chemistry, University of Southern California, Seeley G. Mudd 418, 3620 McClintock Avenue, Los Angeles, California 90089-1062, USA
Biochemistry 45:7036-48. 2006..advance the understanding of catalytic control, we analyze the effect of the protein residues, taking human DNA polymerase beta as a model system...
An SNF2 protein associated with nuclear RNA silencing and the spread of a silencing signal between cells in ArabidopsisLisa 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...
The accumulation of MMS-induced single strand breaks in G1 phase is recombinogenic in DNA polymerase beta defective mammalian cellsBarbara 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...
DNA polymerase lambda mediates a back-up base excision repair activity in extracts of mouse embryonic fibroblastsElena 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...
Neonatal lethality with abnormal neurogenesis in mice deficient in DNA polymerase betaN 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. 2000b>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...
Expanding the repertoire of DNA polymerase substrates: template-instructed incorporation of non-nucleoside triphosphate analogues by DNA polymerases beta and lambdaEmmanuele Crespan
Istituto di Genetica Molecolare, IGM CNR, via Abbiategrasso 207, I 27100 Pavia, Italy
Nucleic Acids Res 35:45-57. 2007..Therefore, this NNTP analog can be considered as the prototype of an entirely novel class of DNA pol substrates...
Poly(ADP-ribose) polymerase-1 protects excessive DNA strand breaks from deterioration during repair in human cell extractsJason 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...
Nucleotide excision repair DNA synthesis by excess DNA polymerase beta: a potential source of genetic instability in cancer cellsY Canitrot
Groupe Instabilité Génétique et Cancer, Groupe Toxico résistance, Institut de Pharmacologie et de Biologie Structurale, CNRS UMR 5089, 31077 Toulouse Cedex 4, France
FASEB J 14:1765-74. 2000..DNA templates, we measured in vitro that extracts from cells overexpressing the error-prone DNA polymerase beta exhibited a five- to sixfold increase of the ultimate DNA synthesis activity compared with control extracts ..
XRCC1 and DNA polymerase beta in cellular protection against cytotoxic DNA single-strand breaksJulie 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 ..
Vertebrate POLQ and POLbeta cooperate in base excision repair of oxidative DNA damageMichio 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...
Subtle but variable conformational rearrangements in the replication cycle of Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4) may accommodate lesion bypassYanli Wang
Department of Chemistry and Courant Institute of Mathematical Sciences, New York University, 251 Mercer Street, New York, NY 10012 2005, USA
Protein Sci 15:135-51. 2006....
Role of XRCC1 in the coordination and stimulation of oxidative DNA damage repair initiated by the DNA glycosylase hOGG1Stéphanie Marsin
Departement de Radiobiologie et Radiopathologie, UMR 217 CNRS, Commissariat a l Energie Atomique, BP6, F 92265 Fontenay aux Roses, France
J Biol Chem 278:44068-74. 2003..process of oxidized purines to yield an APE1-cleaved abasic site, which can be used as a substrate by DNA polymerase beta. More importantly, the results unveil a highly coordinated mechanism by which XRCC1, through its multiple ..
Suppressed catalytic activity of base excision repair enzymes on rotationally positioned uracil in nucleosomesBrian C Beard
Department of Biochemistry and Biophysics, School of Molecular Biosciences, Washington State University, Pullman, WA 99164-4660, USA
Proc Natl Acad Sci U S A 100:7465-70. 2003..was developed that uses human uracil DNA glycosylase (UDG), apyrimidinic/apurinic endonuclease (APE), and DNA polymerase beta (pol beta) on homogeneously damaged, rotationally positioned DNA in nucleosomes...
The base substitution fidelity of DNA polymerase beta-dependent single nucleotide base excision repairToshiro Matsuda
Laboratory of Molecular Genetics and Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
J Biol Chem 278:25947-51. 2003..When human uracil DNA glycosylase, AP endonuclease, DNA polymerase beta, and DNA ligase 1 replace uracil opposite template A or G, base substitution error rates are <or=0...
Induction of DNA polymerase beta-dependent base excision repair in response to oxidative stress in vivoDiane C Cabelof
Department of Nutrition and Food Science, 3009 Science Hall, Wayne State University, Detroit, MI 48202, USA
Carcinogenesis 23:1419-25. 2002..Strong evidence supports the requirement of DNA polymerase beta (beta-pol) in the BER pathway involving single nucleotide gap filling DNA synthesis in mammalian systems...
Human DNA polymerase lambda possesses terminal deoxyribonucleotidyl transferase activity and can elongate RNA primers: implications for novel functionsKristijan Ramadan
Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich Irchel, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
J Mol Biol 328:63-72. 2003..dependent polymerase activity, a distributive manner of DNA synthesis and sequence similarity to DNA polymerase beta suggested a novel beta-like enzyme...
Thermostable DNA polymerases can perform translesion synthesis using 8-oxoguanine and tetrahydrofuran-containing DNA templatesEkaterina A Belousova
Institute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, Lavrentieva Prospect 8, Novosibirsk 630090, Russia
Biochim Biophys Acta 1764:97-104. 2006..Measurements with human DNA polymerase beta were used as a "positive control"...
Structural analysis of strand misalignment during DNA synthesis by a human DNA polymeraseMiguel Garcia-Diaz
Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA
Cell 124:331-42. 2006..They are thus relevant to the origin of single-base deletions, a class of mutations that can confer strong biological phenotypes...
Base excision repair fidelity in normal and cancer cellsKatie K L Chan
Radiation and Genome Stability Unit, Medical Research Council Harwell, Oxfordshire, UK
Mutagenesis 21:173-8. 2006....
ATP-dependent selection between single nucleotide and long patch base excision repairEva Petermann
, , Thielallee 63, 14195, Berlin, Germany
DNA Repair (Amst) 2:1101-14. 2003..Simultaneously, single nucleotide repair is reduced. Rather, the number of nucleotides incorporated by DNA polymerase beta (Pol beta) during DNA repair synthesis is increased...
Efficiency of extension of mismatched primer termini across from cisplatin and oxaliplatin adducts by human DNA polymerases beta and eta in vitroEkaterina Bassett
Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7260, USA
Biochemistry 42:14197-206. 2003..On the other hand, pol beta is more likely to misinsert at the 3'G of the adducts and misinsertion occurs at higher frequency for oxaliplatin-GG than for cisplatin-GG adducts...
In vitro effects of a C4'-oxidized abasic site on DNA polymerasesMarc M Greenberg
Department of Chemistry, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA
Biochemistry 43:2656-63. 2004..The interaction between bypass polymerases and a C4-AP lesion could explain the high levels of G:C --> T:A transversions in cells treated with bleomycin...
A role for polymerase eta in the cellular tolerance to cisplatin-induced damageMark R Albertella
KuDOS Pharmaceuticals Ltd, Cambridge Science Park, Cambridge, UK
Cancer Res 65:9799-806. 2005..Together, these data show that pol eta represents an important determinant of cellular responses to cisplatin, which could have implications for acquired or intrinsic resistance to this key chemotherapeutic agent...
Human DNA polymerases lambda and beta show different efficiencies of translesion DNA synthesis past abasic sites and alternative mechanisms for frameshift generationGiuseppina Blanca
Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique, 205 route de Narbonne, 31077 Toulouse Cedex, France
Biochemistry 43:11605-15. 2004....
Regulation of WRN helicase activity in human base excision repairByungchan Ahn
Department of Life Sciences, University of Ulsan, Ulsan 680 749, Korea
J Biol Chem 279:53465-74. 2004..WRN interacts with DNA polymerase beta (pol beta) and stimulates pol beta strand displacement synthesis on a base excision repair (BER) ..
The human Rad9/Rad1/Hus1 damage sensor clamp interacts with DNA polymerase beta and increases its DNA substrate utilisation efficiency: implications for DNA repairMagali Toueille
Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich Irchel, Wintherturerstrasse 190, CH 8057, Zurich, Switzerland
Nucleic Acids Res 32:3316-24. 2004..In this work, we showed that the 9-1-1 complex can physically interact with DNA polymerase beta in vitro...
Imbalanced base excision repair in response to folate deficiency is accelerated by polymerase beta haploinsufficiencyDiane C Cabelof
Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USA
J Biol Chem 279:36504-13. 2004..05). However, no up-regulation in either BER or its rate-determining enzyme, DNA polymerase beta (beta-pol) is observed in response to folate deficiency...
Ischemic preconditioning in the rat brain enhances the repair of endogenous oxidative DNA damage by activating the base-excision repair pathwayWenjin Li
Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA
J Cereb Blood Flow Metab 26:181-98. 2006..These results suggest that the activation of the BER pathway may contribute to IP-induced neuroprotection by enhancing the repair of endogenous oxidative DNA damage after ischemic injury...
The DNA polymerase lambda is required for the repair of non-compatible DNA double strand breaks by NHEJ in mammalian cellsJean-Pascal Capp
Equipe, , Institut de Pharmacologie et de Biologie Structurale, UMR CNRS 5089, 205 route de Narbonne, 31077 Toulouse, France
Nucleic Acids Res 34:2998-3007. 2006..Our data support a requirement for pollambda in repairing a subset of DSB in genomic DNA, thereby contributing to the maintenance of genetic stability mediated by the NHEJ pathway...
Critical role of magnesium ions in DNA polymerase beta's closing and active site assemblyLinjing Yang
Department of Chemistry and Courant Institute of Mathematical Sciences, New York University, 251 Mercer Street, New York, New York 10012, USA
J Am Chem Soc 126:8441-53. 2004....
Repair of tandem base lesions in DNA by human cell extracts generates persisting single-strand breaksHelen Budworth
MRC Radiation and Genome Stability Unit, Harwell, Oxfordshire OX11 0RD, UK
J Mol Biol 351:1020-9. 2005..Although the presence of the 8-oxoguanine residue near the 3' terminus did not affect either DNA polymerase beta activity or poly(ADP)ribose polymerase-1 affinity and turnover on an incised AP site, we find that 8-..
Saving the ends for last: the role of pol mu in DNA end joiningTanya T Paull
Department of Molecular Genetics and Microbiology, University of Texas at Austin, 1 University Station, A4800, Austin, Texas 78712, USA
Mol Cell 19:294-6. 2005..2005) clarifies the role of pol mu in end joining at the kappa light chain locus and also provides a biochemical explanation for the unique polymerization functions of pol mu on DNA ends...
A gradient of template dependence defines distinct biological roles for family X polymerases in nonhomologous end joiningStephanie A Nick McElhinny
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
Mol Cell 19:357-66. 2005..This apparent gradient of template dependence is largely attributable to a small structural element that is present but different in all three polymerases...
Structural insight into the DNA polymerase beta deoxyribose phosphate lyase mechanismRajendra Prasad
Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, NC 27709, USA
DNA Repair (Amst) 4:1347-57. 2005A large number of biochemical and genetic studies have demonstrated the involvement of DNA polymerase beta (Pol beta) in mammalian base excision repair (BER)...
Snapshots of replication through an abasic lesion; structural basis for base substitutions and frameshiftsHong Ling
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Mol Cell 13:751-62. 2004..In addition, the structure of an unproductive Dpo4 ternary complex suggests that the flexible little finger domain facilitates DNA orientation and translocation during translesion synthesis...
Activities and mechanism of DNA polymerase betaWilliam A Beard
Enzymology Section, Laboratory of Structural Biology, NIEHS-NIH, North Carolina, USA
Methods Enzymol 408:91-107. 2006b>DNA polymerase beta plays an essential role in the base excision repair pathway necessary to cleanse the genome of simple base lesions and abasic sites...
Analysis of base excision DNA repair of the oxidative lesion 2-deoxyribonolactone and the formation of DNA-protein cross-linksJung-Suk Sung
Department of Biology, Dongguk University, Seoul, South Korea
Methods Enzymol 408:48-64. 2006..However, the second enzyme of the canonical BER pathway, DNA polymerase beta, instead of excising Ape1-incised dL, forms a stable DNA-protein cross-link with the lesion...
Human DNA polymerase iota protects cells against oxidative stressTirzah Braz Petta
Centre National de la Recherche Scientifique FRE2939, Unit of genetic stability and oncogenesis, Institut Gustave Roussy, Universite Paris Sud, Villejuif, France
EMBO J 27:2883-95. 2008..This recruitment is partially mediated by its dRP lyase domain and ubiquitin-binding domains. These data reveal a novel role of human poliota in protecting cells from oxidative damage...
Repair of clustered DNA lesions. Sequence-specific inhibition of long-patch base excision repair be 8-oxoguanineHelen Budworth
Medical Research Council Radiation and Genome Stability Unit, Harwell, Oxfordshire OX11 0RD, United Kingdom
J Biol Chem 277:21300-5. 2002..located opposite to an abasic site does not affect either the efficiency or fidelity of repair synthesis by DNA polymerase beta. In contrast, an 8-oxoguanine located one nucleotide 3'-downstream of the abasic site significantly reduces ..
X-rays induce distinct patterns of somatic mutation in fetal versus adult hematopoietic cellsLi Liang
Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, United States
DNA Repair (Amst) 6:1380-5. 2007..activity was significantly lower in fetal hematopoietic cells than in adult cells, due to a low level of DNA polymerase beta, the rate-limiting enzyme in BER...
The processivity factor beta controls DNA polymerase IV traffic during spontaneous mutagenesis and translesion synthesis in vivoNathalie Lenne-Samuel
Institut de Recherche contre les Cancers de l Appareil Digestif, UPR conventionnée de l Université Louis Pasteur de Strasbourg, Hôpitaux Universitaires BP424, 67091 Strasbourg, France
EMBO Rep 3:45-9. 2002..These results point to the pivotal role of the processivity clamp during DNA polymerase trafficking in the vicinity of damaged-template DNA...
Relationship between base excision repair capacity and DNA alkylating agent sensitivity in mouse monocytesK H Chen
Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, TX 77555, USA
Mutat Res 487:121-6. 2001Base excision repair (BER) capacity and the level of DNA polymerase beta (beta-pol) are higher in mouse monocyte cell extracts when cells are treated with oxidative stress-inducing agents...
DNA polymerase beta is the major dRP lyase involved in repair of oxidative base lesions in DNA by mammalian cell extractsS L Allinson
MRC Radiation and Genome Stability Unit, Harwell, Oxfordshire OX11 0RD, UK
EMBO J 20:6919-26. 2001..b>DNA polymerase beta (Pol beta) was implicated recently as the major polymerase involved in repair of oxidative base lesions; ..
The mechanism of switching among multiple BER pathwaysE Dogliotti
Laboratory of Comparative Toxicology and Ecotoxicology, , Viale Regina Elena 299, 00161 Rome, Italy
Prog Nucleic Acid Res Mol Biol 68:3-27. 2001..These findings raise the interesting possibility that different BER pathways might be acting as a function of the cell cycle stage...
Base excision repair in nuclear and mitochondrial DNAG L Dianov
Laboratory of Molecular Genetics, National Institute on Aging, NIH Baltimore, Maryland 21224, USA
Prog Nucleic Acid Res Mol Biol 68:285-97. 2001..Extension of these studies suggests that DNA polymerase beta plays a critical role not only in the short-patch repair process but also in the long-patch, PCNA-dependent ..
Accessibility of DNA polymerases to repair synthesis during nucleotide excision repair in yeast cell-free extractsX Wu
306 Health Sciences Research Building, Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536, USA
Nucleic Acids Res 29:3123-30. 2001..These results suggest that efficient repair synthesis of yeast NER requires both Poldelta and Polvarepsilon in vitro, and that the low fidelity Poleta is not accessible to repair synthesis during NER...
Mechanism of abasic lesion bypass catalyzed by a Y-family DNA polymeraseKevin A Fiala
Department of Biochemistry, The Ohio State Biochemistry Program, The Comprehensive Cancer Center, Ohio State University, Columbus 43210, USA
J Biol Chem 282:8188-98. 2007..Our results suggest that abasic lesion bypass requires tight regulation to maintain genomic stability...
Sloppy bypass of an abasic lesion catalyzed by a Y-family DNA polymeraseKevin A Fiala
Department of Biochemistry, The Ohio State Biochemistry Program, The Comprehensive Cancer Center, Ohio State University, Columbus 43210, USA
J Biol Chem 282:8199-206. 2007..Our results demonstrate that an abasic lesion causes Dpo4 and possibly all Y-family members to switch from a normal to a very mutagenic mode of replication...
Research Grants
- MECHANISM OF BASE EXCISION REPAIR IN HIGHER EUKARYOTESYoshihiro 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...
- RNA-Mediated Silencing: Mechanisms and Biological Roles in ChlamydomonasHeriberto 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 ..
- RNA-Mediated Silencing: Mechanisms and Biological Roles in ChlamydomonasHeriberto 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 ..
- HUMAN DNA REPAIR ENZYMES FOR REDOX AND ALKYLATION DAMAGEBruce 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.
- BIOPHYSICAL AND SCANNING FORCE MICROSCOPY STUDIESDOROTHY 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, ..
- FUNCTION OF PCNA IN CELLULAR DNA REPAIRYoshihiro Matsumoto; Fiscal Year: 2001..In the past, base excision repair was thought to proceed exclusively by a DNA polymerase beta (pol beta)-dependent pathway...
- ROLES OF DNA LIGASE I IN MAMMALIAN DNA METABOLISMAlan 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...
- HUMAN DNA REPAIR ENZYMES FOR REDOX AND ALKYLATION DAMAGEBRUCE 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 ..
- HUMAN DNA REPAIR ENZYMES FOR REDOX AND ALKYLATION DAMAGEBruce 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 ..
- MUTATIONAL MECHANISMS OF REPETITIVE DNA IN HUMAN CELLSKristin 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...
- Base excision repair in zebrafish developmentPHYLLIS STRAUSS; Fiscal Year: 2007..These studies will help define the role of BER in embryogenesis and open a new field of inquiry. ..
- MECHANISMS OF FIDELITY AND MUTAGENESISThomas 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 ..
- Folate Deficiency and Susceptibility to GI DiseaseAHMAD HEYDARI; Fiscal Year: 2003..The model of BER deficiency used in these studies is the DNA polymerase Beta heterozygous knockout mouse...
- AN ENVIRONMENTALLY RELEVANT DNA POL BETA VARIANTSipra Banerjee; Fiscal Year: 2003For 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 ..
- Transcription coupled repair of oxidative DNA damageBRETT 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...
- The Effect of Mre11/Rad50on Fidelity of Synthesis by DNA Polymerase BetaDrew 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 ..
- Base Excision Repair, Genetic Integrity & Health SpanCHRISTI 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...
- HUMAN XRCC1 PROTEIN IN DNA REPAIR AND RECOMBINATIONMICHAEL 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...
- NMR STRUCTURAL OF DNA POLYMERASE BMark Maciejewski; Fiscal Year: 2003Mammalian 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...
