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. Xing G, Kirouac K, Shin Y, Bell S, Ling H. Structural insight into recruitment of translesion DNA polymerase Dpo4 to sliding clamp PCNA. Mol Microbiol. 2009;71:678-91 pubmed publisher
  2. Brenlla A, Markiewicz R, Rueda D, Romano L. Nucleotide selection by the Y-family DNA polymerase Dpo4 involves template translocation and misalignment. Nucleic Acids Res. 2014;42:2555-63 pubmed publisher
    ..This structure provides evidence for a Dpo4 mutagenesis pathway involving a transient misalignment mechanism. ..
  3. Anarbaev R, Rogozina A, Lavrik O. DNA polymerase beta reveals enhanced activity and processivity in reverse micelles. Biophys Chem. 2009;141:11-20 pubmed publisher
    ..the different hydration and confinement effects on activity, processivity, and stability of mammalian DNA polymerase beta in reverse micelles...
  4. Wei W, Englander E. DNA polymerase beta-catalyzed-PCNA independent long patch base excision repair synthesis: a mechanism for repair of oxidatively damaged DNA ends in post-mitotic brain. J Neurochem. 2008;107:734-44 pubmed publisher
    ..THF at this position is refractory to DNA polymerase beta 5'-deoxyribose 5-phosphate lyase activity and drives repair into the LP-BER subpathway...
  5. Sucato C, Upton T, Kashemirov B, Osuna J, Oertell K, Beard W, et al. DNA polymerase beta fidelity: halomethylene-modified leaving groups in pre-steady-state kinetic analysis reveal differences at the chemical transition state. Biochemistry. 2008;47:870-9 pubmed
    The mechanism of DNA polymerase beta-catalyzed nucleotidyl transfer consists of chemical steps involving primer 3' OH deprotonation, nucleophilic attack, and pyrophosphate leaving-group elimination, preceded by dNTP binding which induces ..
  6. Wang Y, Reddy S, Beard W, Wilson S, Schlick T. Differing conformational pathways before and after chemistry for insertion of dATP versus dCTP opposite 8-oxoG in DNA polymerase beta. Biophys J. 2007;92:3063-70 pubmed
    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-..
  7. Eckenroth B, Towle Weicksel J, Sweasy J, DOUBLIE S. The E295K cancer variant of human polymerase ? favors the mismatch conformational pathway during nucleotide selection. J Biol Chem. 2013;288:34850-60 pubmed publisher
    ..Comparison with published structures provides insight into the structural rearrangements within pol ? that occur during the process of nucleotide discrimination. ..
  8. Martín M, Garcia Ortiz M, Esteban V, Blanco L. Ribonucleotides and manganese ions improve non-homologous end joining by human Pol?. Nucleic Acids Res. 2013;41:2428-36 pubmed publisher
  9. Liu Y, Wilson S. DNA base excision repair: a mechanism of trinucleotide repeat expansion. Trends Biochem Sci. 2012;37:162-72 pubmed publisher

More Information

Publications62

  1. Sukhanova M, Khodyreva S, Lavrik O. Poly(ADP-ribose) polymerase 1 regulates activity of DNA polymerase beta in long patch base excision repair. Mutat Res. 2010;685:80-9 pubmed publisher
    ..and model BER DNA intermediates, we examined the influence of PARP1 and its autopoly(ADP-ribosyl)ation on DNA polymerase beta (Pol beta)-mediated long patch (LP) BER DNA synthesis that is accomplished through a cooperation between ..
  2. DeCarlo L, Gowda A, Suo Z, Spratt T. Formation of purine-purine mispairs by Sulfolobus solfataricus DNA polymerase IV. Biochemistry. 2008;47:8157-64 pubmed publisher
    ..This result may be functionally relevant in the replication of damaged DNA in that the polymerase may allow the template to adopt multiple configurations...
  3. Gembka A, Toueille M, Smirnova E, Poltz R, Ferrari E, Villani G, et al. 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. Nucleic Acids Res. 2007;35:2596-608 pubmed
    ..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 ..
  4. Garcia Diaz M, Bebenek K, Krahn J, Pedersen L, Kunkel T. Role of the catalytic metal during polymerization by DNA polymerase lambda. DNA Repair (Amst). 2007;6:1333-40 pubmed
    ..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. ..
  5. Lai Y, Zhao W, Chen C, Wu M, Zhang Z. Role of DNA polymerase beta in the genotoxicity of arsenic. Environ Mol Mutagen. 2011;52:460-8 pubmed publisher
    ..As a critical repair enzyme in BER, DNA polymerase beta (Pol ?) might play an essential role in reducing arsenic toxicity...
  6. Tano K, Nakamura J, Asagoshi K, Arakawa H, Sonoda E, Braithwaite E, et al. Interplay between DNA polymerases beta and lambda in repair of oxidation DNA damage in chicken DT40 cells. DNA Repair (Amst). 2007;6:869-75 pubmed
    DNA polymerase lambda (Pol lambda) is a DNA polymerase beta (Pol beta)-like enzyme with both DNA synthetic and 5'-deoxyribose-5'-phosphate lyase domains...
  7. Akopiants K, Zhou R, Mohapatra S, Valerie K, Lees Miller S, Lee K, et al. Requirement for XLF/Cernunnos in alignment-based gap filling by DNA polymerases lambda and mu for nonhomologous end joining in human whole-cell extracts. Nucleic Acids Res. 2009;37:4055-62 pubmed publisher
    ..Thus, Cernunnos is essential for gap filling by either polymerase during nonhomologous end joining, suggesting that it plays a major role in aligning the two DNA ends in the repair complex. ..
  8. Michiels S, Laplanche A, Boulet T, Dessen P, Guillonneau B, Mejean A, et al. Genetic polymorphisms in 85 DNA repair genes and bladder cancer risk. Carcinogenesis. 2009;30:763-8 pubmed publisher
    ..It is anticipated that genome-wide association studies will open new perspectives for interpretation of the results of extensive candidate gene studies such as ours. ..
  9. Stachelek G, Dalal S, Donigan K, Campisi Hegan D, Sweasy J, Glazer P. Potentiation of temozolomide cytotoxicity by inhibition of DNA polymerase beta is accentuated by BRCA2 mutation. Cancer Res. 2010;70:409-17 pubmed publisher
    ..We investigated the effects of lithocholic acid (LCA), an inhibitor of the key BER enzyme DNA polymerase beta (pol beta), in cells deficient in expression of the homology-dependent repair factor BRCA2...
  10. Prakasha Gowda A, Polizzi J, Eckert K, Spratt T. Incorporation of gemcitabine and cytarabine into DNA by DNA polymerase beta and ligase III/XRCC1. Biochemistry. 2010;49:4833-40 pubmed publisher
    ..Ligation efficiency by T4 ligase and ligase III/XRCC1 was largely unaffected by the nucleotide analogues. Our results show that BER is capable of incorporating araC and dFdC into the genome. ..
  11. Maga G, Crespan E, Wimmer U, van Loon B, Amoroso A, Mondello C, et al. Replication protein A and proliferating cell nuclear antigen coordinate DNA polymerase selection in 8-oxo-guanine repair. Proc Natl Acad Sci U S A. 2008;105:20689-94 pubmed publisher
  12. Prasad R, Shock D, Beard W, Wilson S. Substrate channeling in mammalian base excision repair pathways: passing the baton. J Biol Chem. 2010;285:40479-88 pubmed publisher
    ..Instead, flap endonuclease 1 must recognize and bind to the intermediate in competition with other molecules. ..
  13. Allen D, Herbert D, McMahan C, Rotrekl V, Sobol R, Wilson S, et al. Mutagenesis is elevated in male germ cells obtained from DNA polymerase-beta heterozygous mice. Biol Reprod. 2008;79:824-31 pubmed publisher
    ..Notably, spermatogenic cells respond differently than somatic cells to Polb haploinsufficiency. ..
  14. Wang Y, Musser S, Saleh S, Marnett L, Egli M, Stone M. Insertion of dNTPs opposite the 1,N2-propanodeoxyguanosine adduct by Sulfolobus solfataricus P2 DNA polymerase IV. Biochemistry. 2008;47:7322-34 pubmed publisher
    ..These results provide insight into how -1 frameshift mutations might be generated for the PdG adduct, a structural model for the exocylic M 1dG adduct formed by malondialdehyde...
  15. Wang Y, Schlick T. Distinct energetics and closing pathways for DNA polymerase beta with 8-oxoG template and different incoming nucleotides. BMC Struct Biol. 2007;7:7 pubmed
    ..8-oxoG) is a common oxidative lesion frequently encountered by DNA polymerases such as the repair enzyme DNA polymerase beta (pol beta)...
  16. Tang K, Niebuhr M, Tung C, Chan H, Chou C, Tsai M. Mismatched dNTP incorporation by DNA polymerase beta does not proceed via globally different conformational pathways. Nucleic Acids Res. 2008;36:2948-57 pubmed publisher
    ..SAXS) and structural modeling to probe the conformations of different intermediate states of mammalian DNA polymerase beta (Pol beta) in its wild-type and an error-prone variant, I260Q...
  17. Lai Y, Xu M, Zhang Z, Liu Y. Instability of CTG repeats is governed by the position of a DNA base lesion through base excision repair. PLoS ONE. 2013;8:e56960 pubmed publisher
    ..Our study indicates that the position of a DNA base lesion governs whether TNR is expanded or deleted through BER. ..
  18. Lin P, Batra V, Pedersen L, Beard W, Wilson S, Pedersen L. Incorrect nucleotide insertion at the active site of a G:A mismatch catalyzed by DNA polymerase beta. Proc Natl Acad Sci U S A. 2008;105:5670-4 pubmed publisher
    Based on a recent ternary complex crystal structure of human DNA polymerase beta with a G:A mismatch in the active site, we carried out a theoretical investigation of the catalytic mechanism of incorrect nucleotide incorporation using ..
  19. Maul R, Ponticelli S, Duzen J, Sutton M. Differential binding of Escherichia coli DNA polymerases to the beta-sliding clamp. Mol Microbiol. 2007;65:811-27 pubmed
    ..Taken together, these findings indicate that pol II, pol III and pol IV interact with distinct, albeit overlapping surfaces of the beta clamp. ..
  20. Schrader C, Guikema J, Wu X, Stavnezer J. The roles of APE1, APE2, DNA polymerase beta and mismatch repair in creating S region DNA breaks during antibody class switch. Philos Trans R Soc Lond B Biol Sci. 2009;364:645-52 pubmed publisher
    ..We also investigate whether DNA polymerase beta, which correctly repairs SSBs resulting from APE activity, attempts to repair the breaks during CSR...
  21. Lin G, Jaeger J, Sweasy J. Loop II of DNA polymerase beta is important for polymerization activity and fidelity. Nucleic Acids Res. 2007;35:2924-35 pubmed
    ..We use DNA polymerase beta (pol beta) as a model system to investigate mechanisms of preserving fidelity during nucleotide ..
  22. Brown J, Duym W, Fowler J, Suo Z. Single-turnover kinetic analysis of the mutagenic potential of 8-oxo-7,8-dihydro-2'-deoxyguanosine during gap-filling synthesis catalyzed by human DNA polymerases lambda and beta. J Mol Biol. 2007;367:1258-69 pubmed
    ..Employing single-turnover kinetic methods, we examined human DNA polymerase beta and its novel X-family homolog, human DNA polymerase lambda, to determine which nucleotide and template ..
  23. Tang K, Niebuhr M, Aulabaugh A, Tsai M. Solution structures of 2 : 1 and 1 : 1 DNA polymerase-DNA complexes probed by ultracentrifugation and small-angle X-ray scattering. Nucleic Acids Res. 2008;36:849-60 pubmed
    ..X-ray scattering (SAXS) and sedimentation velocity (SV) studies on the enzyme-DNA complexes of rat DNA polymerase beta (Pol beta) and African swine fever virus DNA polymerase X (ASFV Pol X) with one-nucleotide gapped DNA...
  24. Trivedi R, Wang X, Jelezcova E, Goellner E, Tang J, Sobol R. Human methyl purine DNA glycosylase and DNA polymerase beta expression collectively predict sensitivity to temozolomide. Mol Pharmacol. 2008;74:505-16 pubmed publisher
    ..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...
  25. Heltzel J, Maul R, Scouten Ponticelli S, Sutton M. A model for DNA polymerase switching involving a single cleft and the rim of the sliding clamp. Proc Natl Acad Sci U S A. 2009;106:12664-9 pubmed publisher
    ..Taken together, our findings challenge the toolbelt model and suggest instead that Pol IV contacts the rim of the clamp adjacent to the cleft that is bound by Pol III* before gaining control of the same cleft that is bound by Pol III*. ..
  26. Guo Z, Zheng L, Dai H, Zhou M, Xu H, Shen B. Human DNA polymerase beta polymorphism, Arg137Gln, impairs its polymerase activity and interaction with PCNA and the cellular base excision repair capacity. Nucleic Acids Res. 2009;37:3431-41 pubmed publisher
    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...
  27. McKenna C, Kashemirov B, Upton T, Batra V, Goodman M, Pedersen L, et al. (R)-beta,gamma-fluoromethylene-dGTP-DNA ternary complex with DNA polymerase beta. J Am Chem Soc. 2007;129:15412-3 pubmed
  28. Batra V, Pedersen L, Beard W, Wilson S, Kashemirov B, Upton T, et al. Halogenated beta,gamma-methylene- and ethylidene-dGTP-DNA ternary complexes with DNA polymerase beta: structural evidence for stereospecific binding of the fluoromethylene analogues. J Am Chem Soc. 2010;132:7617-25 pubmed publisher
    ..at the CHF carbon, as in beta,gamma-fluoromethylene-dGTP, which forms an active site complex with DNA polymerase beta, a repair enzyme that plays an important role in base excision repair (BER) and oncogenesis...
  29. Cisneros G, Perera L, Garcia Diaz M, Bebenek K, Kunkel T, Pedersen L. Catalytic mechanism of human DNA polymerase lambda with Mg2+ and Mn2+ from ab initio quantum mechanical/molecular mechanical studies. DNA Repair (Amst). 2008;7:1824-34 pubmed publisher
    ..There is partial conservation of these residues across the Pol X family of DNA polymerases. ..
  30. Yamtich J, Nemec A, Keh A, Sweasy J. A germline polymorphism of DNA polymerase beta induces genomic instability and cellular transformation. PLoS Genet. 2012;8:e1003052 pubmed publisher
    ..Our results suggest that people who carry the rs3136797 germline SNP may be at an increased risk for cancer susceptibility...
  31. Yamtich J, Speed W, Straka E, Kidd J, Sweasy J, Kidd K. Population-specific variation in haplotype composition and heterozygosity at the POLB locus. DNA Repair (Amst). 2009;8:579-84 pubmed publisher
    b>DNA polymerase beta plays a central role in base excision repair (BER), which removes large numbers of endogenous DNA lesions from each cell on a daily basis...
  32. Markkanen E, van Loon B, Ferrari E, Parsons J, Dianov G, Hubscher U. Regulation of oxidative DNA damage repair by DNA polymerase ? and MutYH by cross-talk of phosphorylation and ubiquitination. Proc Natl Acad Sci U S A. 2012;109:437-42 pubmed publisher
    ..Finally, MutYH appears to promote the stability of Pol ? by binding it to chromatin. In contrast, Pol ? not engaged in active repair on chromatin is subject for proteasomal degradation. ..
  33. Liu Y, Prasad R, Beard W, Kedar P, Hou E, Shock D, et al. Coordination of steps in single-nucleotide base excision repair mediated by apurinic/apyrimidinic endonuclease 1 and DNA polymerase beta. J Biol Chem. 2007;282:13532-41 pubmed
    ..DNA binding specificities of two major human SN-BER enzymes, apurinic/aprymidinic endonuclease 1 (APE) and DNA polymerase beta (Pol beta). It is known that these enzymes do not form a stable complex in solution...
  34. Chan K, Houlbrook S, Zhang Q, Harrison M, Hickson I, Dianov G. Overexpression of DNA polymerase beta results in an increased rate of frameshift mutations during base excision repair. Mutagenesis. 2007;22:183-8 pubmed
    b>DNA polymerase beta (Pol beta) is important for the base excision repair (BER) pathway. Overexpression of Pol beta is frequently found in cancer cells and is thought to be associated with tumorigenesis...
  35. van Loon B, Hubscher U. An 8-oxo-guanine repair pathway coordinated by MUTYH glycosylase and DNA polymerase lambda. Proc Natl Acad Sci U S A. 2009;106:18201-6 pubmed publisher
    ..These results reveal a cellular response pathway to ROS, important to sustain genomic stability and modulate carcinogenesis. ..
  36. Asagoshi K, Liu Y, Masaoka A, Lan L, Prasad R, Horton J, et al. DNA polymerase beta-dependent long patch base excision repair in living cells. DNA Repair (Amst). 2010;9:109-19 pubmed publisher
    We examined a role for DNA polymerase beta (Pol beta) in mammalian long patch base excision repair (LP BER)...
  37. Alberts I, Wang Y, Schlick T. DNA polymerase beta catalysis: are different mechanisms possible?. J Am Chem Soc. 2007;129:11100-10 pubmed
    ..Mammalian DNA polymerase beta (pol beta), a small (39 kDa) member of the X-family, represents an excellent model system to investigate ..
  38. MURPHY D, Donigan K, Jaeger J, Sweasy J. The E288K colon tumor variant of DNA polymerase ? is a sequence specific mutator. Biochemistry. 2012;51:5269-75 pubmed
    ..This may explain the reduced degree of discrimination at the level of nucleotide binding. The enhanced mutagenesis of the E288K variant could lead to genomic instability and ultimately a malignant tumor phenotype. ..
  39. Donigan K, Sun K, Nemec A, MURPHY D, Cong X, Northrup V, et al. Human POLB gene is mutated in high percentage of colorectal tumors. J Biol Chem. 2012;287:23830-9 pubmed publisher
    ..Such compromised base excision repair may drive tumorigenesis by leading to an increase in mutagenesis or genomic instability. ..
  40. Kidane D, Dalal S, Keh A, Liu Y, Zelterman D, Sweasy J. DNA polymerase beta is critical for genomic stability of sperm cells. DNA Repair (Amst). 2011;10:390-7 pubmed publisher
    ..A key enzyme that functions in this repair pathway is DNA polymerase beta (Pol ?)...
  41. Roettger M, Bakhtina M, Tsai M. Mismatched and matched dNTP incorporation by DNA polymerase beta proceed via analogous kinetic pathways. Biochemistry. 2008;47:9718-27 pubmed publisher
    While matched nucleotide incorporation by DNA polymerase beta (Pol beta) has been well-studied, a true understanding of polymerase fidelity requires comparison of both matched and mismatched dNTP incorporation pathways...
  42. Kidane D, Jonason A, Gorton T, Mihaylov I, Pan J, Keeney S, et al. DNA polymerase beta is critical for mouse meiotic synapsis. EMBO J. 2010;29:410-23 pubmed publisher
    We have shown earlier that DNA polymerase beta (Pol beta) localizes to the synaptonemal complex (SC) during Prophase I of meiosis in mice...
  43. Di Pasquale F, Fischer D, Grohmann D, Restle T, Geyer A, Marx A. Opposed steric constraints in human DNA polymerase beta and E. coli DNA polymerase I. J Am Chem Soc. 2008;130:10748-57 pubmed publisher
    ..at the 3'-terminal position as steric probes to investigate differential active site properties of human DNA polymerase beta (Pol beta) and the 3'-->5'-exonuclease-deficient Klenow fragment of E. coli DNA polymerase I (KF(exo-))...
  44. Mizushina Y, Manita D, Takeuchi T, Sugawara F, Kumamoto Yonezawa Y, Matsui Y, et al. The inhibitory action of kohamaic acid A derivatives on mammalian DNA polymerase beta. Molecules. 2008;14:102-21 pubmed publisher
    ..The relationship between the three-dimensional molecular structures of KA-A-related compounds and these inhibitory activities is discussed. ..
  45. Bakhtina M, Roettger M, Tsai M. Contribution of the reverse rate of the conformational step to polymerase beta fidelity. Biochemistry. 2009;48:3197-208 pubmed publisher
    ..Here we use a stopped-flow technique to directly measure the reverse rate of the conformational step in the DNA polymerase beta (Pol beta) kinetic pathway...
  46. Nunthawarasilp P, Petmitr S, Chavalitshewinkoon Petmitr P. Partial purification and characterization of DNA polymerase beta-like enzyme from Plasmodium falciparum. Mol Biochem Parasitol. 2007;154:141-7 pubmed
    ..only three types of DNA polymerases-alpha, gamma, and delta have previously been characterized, whereas DNA polymerase beta, the major enzyme operating during base excision repair in eukaryotes, has yet to be isolated and ..
  47. Dalal S, Chikova A, Jaeger J, Sweasy J. The Leu22Pro tumor-associated variant of DNA polymerase beta is dRP lyase deficient. Nucleic Acids Res. 2008;36:411-22 pubmed
    Approximately 30% of human tumors characterized to date express DNA polymerase beta (pol beta) variant proteins...
  48. Freudenthal B, Beard W, Shock D, Wilson S. Observing a DNA polymerase choose right from wrong. Cell. 2013;154:157-68 pubmed publisher
    ..This appears to be coupled to subdomain repositioning that is required for catalytic activation/deactivation. The structures provide insights into a fundamental chemical reaction that impacts polymerase fidelity and genome stability. ..
  49. Eoff R, Irimia A, Angel K, Egli M, Guengerich F. Hydrogen bonding of 7,8-dihydro-8-oxodeoxyguanosine with a charged residue in the little finger domain determines miscoding events in Sulfolobus solfataricus DNA polymerase Dpo4. J Biol Chem. 2007;282:19831-43 pubmed
    ..These results support the view that a bond between Arg(332) and 8-oxoG plays a role in determining the fidelity and efficiency of Dpo4-catalyzed bypass of the lesion. ..
  50. Wimmer U, Ferrari E, Hunziker P, Hubscher U. Control of DNA polymerase lambda stability by phosphorylation and ubiquitination during the cell cycle. EMBO Rep. 2008;9:1027-33 pubmed publisher
    ..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. ..
  51. Yuan B, Cao H, Jiang Y, Hong H, Wang Y. Efficient and accurate bypass of N2-(1-carboxyethyl)-2'-deoxyguanosine by DinB DNA polymerase in vitro and in vivo. Proc Natl Acad Sci U S A. 2008;105:8679-84 pubmed publisher
    ..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. ..
  52. Batra V, Beard W, Shock D, Pedersen L, Wilson S. Structures of DNA polymerase beta with active-site mismatches suggest a transient abasic site intermediate during misincorporation. Mol Cell. 2008;30:315-24 pubmed publisher
    We report the crystallographic structures of DNA polymerase beta with dG-dAMPCPP and dC-dAMPCPP mismatches in the active site...
  53. Prasad R, Liu Y, Deterding L, Poltoratsky V, Kedar P, Horton J, et al. HMGB1 is a cofactor in mammalian base excision repair. Mol Cell. 2007;27:829-41 pubmed
    Deoxyribose phosphate (dRP) removal by DNA polymerase beta (Pol beta) is a pivotal step in base excision repair (BER)...