dna polymerase ii

Summary

Summary: A DNA-dependent DNA polymerase characterized in E. coli and other lower organisms. It may be present in higher organisms and has an intrinsic molecular activity only 5% of that of DNA Polymerase I. This polymerase has 3'-5' exonuclease activity, is effective only on duplex DNA with gaps or single-strand ends of less than 100 nucleotides as template, and is inhibited by sulfhydryl reagents. EC 2.7.7.7.

Top Publications

  1. Du Z, Liu J, Albracht C, Hsu A, Chen W, Marieni M, et al. Structural and mutational studies of a hyperthermophilic intein from DNA polymerase II of Pyrococcus abyssi. J Biol Chem. 2011;286:38638-48 pubmed publisher
    ..NMR spin relaxation indicates that the Pab PolII intein is significantly more rigid than mesophilic inteins, which may contribute to the higher optimal temperature for protein splicing...
  2. Shimizu K, Hashimoto K, Kirchner J, Nakai W, Nishikawa H, Resnick M, et al. Fidelity of DNA polymerase epsilon holoenzyme from budding yeast Saccharomyces cerevisiae. J Biol Chem. 2002;277:37422-9 pubmed
  3. Feng W, Rodriguez Menocal L, Tolun G, D URSO G. Schizosacchromyces pombe Dpb2 binds to origin DNA early in S phase and is required for chromosomal DNA replication. Mol Biol Cell. 2003;14:3427-36 pubmed
  4. Tsubota T, Maki S, Kubota H, Sugino A, Maki H. Double-stranded DNA binding properties of Saccharomyces cerevisiae DNA polymerase epsilon and of the Dpb3p-Dpb4p subassembly. Genes Cells. 2003;8:873-88 pubmed
    ..One of these sites has a strong affinity for dsDNA, a feature that is not generally associated with DNA polymerases. Involvement of the Dpb3p-Dpb4p complex in the dsDNA-binding of Pol epsilon is inferred. ..
  5. Wang Z, Lazarov E, O Donnell M, Goodman M. Resolving a fidelity paradox: why Escherichia coli DNA polymerase II makes more base substitution errors in AT- compared with GC-rich DNA. J Biol Chem. 2002;277:4446-54 pubmed
    ..Unexpectedly, however, the opposite result was found for Escherichia coli DNA polymerase II (pol II)...
  6. Rangarajan S, Woodgate R, Goodman M. A phenotype for enigmatic DNA polymerase II: a pivotal role for pol II in replication restart in UV-irradiated Escherichia coli. Proc Natl Acad Sci U S A. 1999;96:9224-9 pubmed
    ..At the present time, the molecular mechanism underlying replication restart is not understood. DNA polymerase II (pol II), encoded by the dinA (polB) gene, is induced as part of the global SOS response to DNA damage...
  7. Becherel O, Fuchs R. Mechanism of DNA polymerase II-mediated frameshift mutagenesis. Proc Natl Acad Sci U S A. 2001;98:8566-71 pubmed
    ..Whether such a polymerase competition model for translesion synthesis will prove to be generally applicable remains to be confirmed. ..
  8. Bourbon H. Comparative genomics supports a deep evolutionary origin for the large, four-module transcriptional mediator complex. Nucleic Acids Res. 2008;36:3993-4008 pubmed publisher
    ..The implications of this comprehensive work for MED structure-function relationships are discussed...
  9. Pursell Z, Isoz I, Lundström E, Johansson E, Kunkel T. Regulation of B family DNA polymerase fidelity by a conserved active site residue: characterization of M644W, M644L and M644F mutants of yeast DNA polymerase epsilon. Nucleic Acids Res. 2007;35:3076-86 pubmed

More Information

Publications61

  1. Lee J, Gold D, Shevchenko A, Shevchenko A, Dunphy W. Roles of replication fork-interacting and Chk1-activating domains from Claspin in a DNA replication checkpoint response. Mol Biol Cell. 2005;16:5269-82 pubmed
    ..Another implication of this work is that stable binding of Claspin to chromatin may play a role in other functions besides the activation of Chk1. ..
  2. Ng H, Robert F, Young R, Struhl K. Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity. Mol Cell. 2003;11:709-19 pubmed
  3. Shcherbakova P, Pavlov Y, Chilkova O, Rogozin I, Johansson E, Kunkel T. Unique error signature of the four-subunit yeast DNA polymerase epsilon. J Biol Chem. 2003;278:43770-80 pubmed
    ..We discuss the implications of these findings for the role of Pol epsilon polymerase activity in DNA replication. ..
  4. D URSO G, Nurse P. Schizosaccharomyces pombe cdc20+ encodes DNA polymerase epsilon and is required for chromosomal replication but not for the S phase checkpoint. Proc Natl Acad Sci U S A. 1997;94:12491-6 pubmed
    ..We propose that the checkpoint signal operating in S phase depends on assembly of the replication initiation complex, and that this signal is generated prior to the elongation stage of DNA synthesis. ..
  5. Ohya T, Maki S, Kawasaki Y, Sugino A. Structure and function of the fourth subunit (Dpb4p) of DNA polymerase epsilon in Saccharomyces cerevisiae. Nucleic Acids Res. 2000;28:3846-52 pubmed
    ..cerevisiae, even if it is not essential for cell growth. Structural homologues of DPB4 are present in other eukaryotic genomes, suggesting that the complex structure of S. cerevisiae Polepsilon is conserved in eukaryotes. ..
  6. Vlatkovic N, Guerrera S, Li Y, Linn S, Haines D, Boyd M. MDM2 interacts with the C-terminus of the catalytic subunit of DNA polymerase epsilon. Nucleic Acids Res. 2000;28:3581-6 pubmed
    ..Our studies provide evidence that MDM2 interacts with a region of DNA pol epsilon that plays a critical role in the function of DNA pol epsilon. ..
  7. Nuutinen T, Tossavainen H, Fredriksson K, Pirilä P, Permi P, Pospiech H, et al. The solution structure of the amino-terminal domain of human DNA polymerase epsilon subunit B is homologous to C-domains of AAA+ proteins. Nucleic Acids Res. 2008;36:5102-10 pubmed publisher
    ..The biased distribution of the charged residues is reflected by a polarization and a considerable dipole moment across the Dpoe2NT. Dpoe2NT represents the first C-domain fold not associated with an AAA+ protein. ..
  8. Albertson T, Ogawa M, Bugni J, Hays L, Chen Y, Wang Y, et al. DNA polymerase epsilon and delta proofreading suppress discrete mutator and cancer phenotypes in mice. Proc Natl Acad Sci U S A. 2009;106:17101-4 pubmed publisher
    ..These findings distinguish Pol epsilon and delta functions in vivo and reveal tissue-specific requirements for DNA replication fidelity. ..
  9. Wang H, Elledge S. DRC1, DNA replication and checkpoint protein 1, functions with DPB11 to control DNA replication and the S-phase checkpoint in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1999;96:3824-9 pubmed
    ..DRC1 and DPB11 show synthetic lethality and reciprocal dosage suppression. The Drc1 and Dpb11 proteins physically associate and function together to coordinate DNA replication and the cell cycle. ..
  10. Tran H, Gordenin D, Resnick M. The 3'-->5' exonucleases of DNA polymerases delta and epsilon and the 5'-->3' exonuclease Exo1 have major roles in postreplication mutation avoidance in Saccharomyces cerevisiae. Mol Cell Biol. 1999;19:2000-7 pubmed
    ..Surprisingly, the mutation rate in an exo1 pol3-01 mutant was comparable to that in an msh2 pol3-01 mutant, suggesting that they participate directly in postreplication mismatch repair as well as in other DNA metabolic processes. ..
  11. Lovett S. Replication arrest-stimulated recombination: Dependence on the RecA paralog, RadA/Sms and translesion polymerase, DinB. DNA Repair (Amst). 2006;5:1421-7 pubmed
    ..The role of DinB in bacteria may be analogous to translesion DNA polymerase eta in eukaryotes, recently shown to aid recombination. ..
  12. Suyari O, Kawai M, Ida H, Yoshida H, Sakaguchi K, Yamaguchi M. Differential requirement for the N-terminal catalytic domain of the DNA polymerase ? p255 subunit in the mitotic cell cycle and the endocycle. Gene. 2012;495:104-14 pubmed publisher
    ..In addition, several genetic interactants with dpol?p255 including genes related to DNA replication such as RFC, DNA primase, DNA pol?, Mcm10 and Psf2 and chromatin remodeling such as Iswi were also identified. ..
  13. Aksenova A, Volkov K, Maceluch J, Pursell Z, Rogozin I, Kunkel T, et al. Mismatch repair-independent increase in spontaneous mutagenesis in yeast lacking non-essential subunits of DNA polymerase ?. PLoS Genet. 2010;6:e1001209 pubmed publisher
  14. Yoshida R, Miyashita K, Inoue M, Shimamoto A, Yan Z, Egashira A, et al. Concurrent genetic alterations in DNA polymerase proofreading and mismatch repair in human colorectal cancer. Eur J Hum Genet. 2011;19:320-5 pubmed publisher
    ..Our observations may suggest previously unrecognised complexities in the molecular abnormalities underlying the mutator phenotype in human neoplasms. ..
  15. Kesti T, McDonald W, Yates J, Wittenberg C. Cell cycle-dependent phosphorylation of the DNA polymerase epsilon subunit, Dpb2, by the Cdc28 cyclin-dependent protein kinase. J Biol Chem. 2004;279:14245-55 pubmed
    ..We suggest that phosphorylation of Dpb2 during late G(1) phase at CDK consensus sites facilitates the interaction with Pol2 or the activity of Polepsilon ..
  16. Chilkova O, Jonsson B, Johansson E. The quaternary structure of DNA polymerase epsilon from Saccharomyces cerevisiae. J Biol Chem. 2003;278:14082-6 pubmed
    ..Thus, both DNA polymerase delta and Pol epsilon are purified as monomeric complexes, in agreement with accumulating evidence that Pol delta and Pol epsilon are located on opposite strands of the eukaryotic replication fork. ..
  17. Ishino Y, Komori K, Cann I, Koga Y. A novel DNA polymerase family found in Archaea. J Bacteriol. 1998;180:2232-6 pubmed
    ..Recently, we identified the genes of DNA polymerase II (the second DNA polymerase) from the hyperthermophilic archaeon Pyrococcus furiosus, which has also at least ..
  18. Yankulov K, Todorov I, Romanowski P, Licatalosi D, Cilli K, McCracken S, et al. MCM proteins are associated with RNA polymerase II holoenzyme. Mol Cell Biol. 1999;19:6154-63 pubmed
    ..These results suggest a new function for MCM proteins as components of the Pol II transcriptional apparatus. ..
  19. Ohya T, Kawasaki Y, Hiraga S, Kanbara S, Nakajo K, Nakashima N, et al. The DNA polymerase domain of pol(epsilon) is required for rapid, efficient, and highly accurate chromosomal DNA replication, telomere length maintenance, and normal cell senescence in Saccharomyces cerevisiae. J Biol Chem. 2002;277:28099-108 pubmed
    ..These results indicate that the DNA polymerase domain of Pol2p is required for rapid, efficient, and highly accurate chromosomal DNA replication in yeast. ..
  20. Jaszczur M, Flis K, Rudzka J, Kraszewska J, Budd M, Polaczek P, et al. Dpb2p, a noncatalytic subunit of DNA polymerase epsilon, contributes to the fidelity of DNA replication in Saccharomyces cerevisiae. Genetics. 2008;178:633-47 pubmed publisher
    ..Our results show that DNA polymerase subunits other than those housing the DNA polymerase and 3' --> 5' exonuclease are essential in controlling the level of spontaneous mutagenesis and genetic stability in yeast cells. ..
  21. Gawel D, Pham P, Fijalkowska I, Jonczyk P, Schaaper R. Role of accessory DNA polymerases in DNA replication in Escherichia coli: analysis of the dnaX36 mutator mutant. J Bacteriol. 2008;190:1730-42 pubmed
    ..Overall, the results provide insight into the interplay of the various DNA polymerases, and of tau subunit, in securing a high fidelity of replication. ..
  22. Kirchner J, Tran H, Resnick M. A DNA polymerase epsilon mutant that specifically causes +1 frameshift mutations within homonucleotide runs in yeast. Genetics. 2000;155:1623-32 pubmed
    ..This is the first report of a +1-specific mutator for homonucleotide runs in vivo. The pol2-C1089Y mutation defines a functionally important residue in Polepsilon. ..
  23. Waga S, Masuda T, Takisawa H, Sugino A. DNA polymerase epsilon is required for coordinated and efficient chromosomal DNA replication in Xenopus egg extracts. Proc Natl Acad Sci U S A. 2001;98:4978-83 pubmed
    ..These findings strongly suggest that Pol epsilon, along with Pol alpha and Pol delta, is necessary for coordinated chromosomal DNA replication in eukaryotic cells. ..
  24. Rytkönen A, Vaara M, Nethanel T, Kaufmann G, Sormunen R, Läärä E, et al. Distinctive activities of DNA polymerases during human DNA replication. FEBS J. 2006;273:2984-3001 pubmed
    ..These data are consistent with models where pols delta and epsilon pursue their functions at least partly independently during DNA replication. ..
  25. Iida T, Araki H. Noncompetitive counteractions of DNA polymerase epsilon and ISW2/yCHRAC for epigenetic inheritance of telomere position effect in Saccharomyces cerevisiae. Mol Cell Biol. 2004;24:217-27 pubmed
    ..We therefore propose that inheritance of specific epigenetic states of a telomere requires at least two counteracting regulators. ..
  26. Szulc J, Wiznerowicz M, Sauvain M, Trono D, Aebischer P. A versatile tool for conditional gene expression and knockdown. Nat Methods. 2006;3:109-16 pubmed
    ..These results open up promising perspectives for basic or translational research and for the development of gene-based therapeutics. ..
  27. Handa T, Kanke M, Takahashi T, Nakagawa T, Masukata H. DNA polymerization-independent functions of DNA polymerase epsilon in assembly and progression of the replisome in fission yeast. Mol Biol Cell. 2012;23:3240-53 pubmed publisher
    ..These results demonstrate that Pol ? plays essential roles in both the assembly and progression of CMG helicase...
  28. Hastings P, Hersh M, Thornton P, Fonville N, Slack A, Frisch R, et al. Competition of Escherichia coli DNA polymerases I, II and III with DNA Pol IV in stressed cells. PLoS ONE. 2010;5:e10862 pubmed publisher
    ..This mutagenesis assay reveals the DNA polymerases operating in DSB repair during stress and also provides a sensitive indicator for DNA polymerase competition and choice in vivo. ..
  29. Tsubota T, Tajima R, Ode K, Kubota H, Fukuhara N, Kawabata T, et al. Double-stranded DNA binding, an unusual property of DNA polymerase epsilon, promotes epigenetic silencing in Saccharomyces cerevisiae. J Biol Chem. 2006;281:32898-908 pubmed
    ..We conclude that the dsDNA-binding property of Pol epsilon is required for epigenetic silencing at telomeres. ..
  30. Pai C, Garcia I, Wang S, Cotterill S, MacNeill S, Kearsey S. GINS inactivation phenotypes reveal two pathways for chromatin association of replicative alpha and epsilon DNA polymerases in fission yeast. Mol Biol Cell. 2009;20:1213-22 pubmed publisher
    ..We suggest that GINS functions in a pathway that involves Cdc45 and is necessary for DNA polymerase epsilon chromatin binding, but that a separate pathway sets up the chromatin association of DNA polymerase alpha. ..
  31. Ehrenhofer Murray A, Kamakaka R, Rine J. A role for the replication proteins PCNA, RF-C, polymerase epsilon and Cdc45 in transcriptional silencing in Saccharomyces cerevisiae. Genetics. 1999;153:1171-82 pubmed
    ..Restoration of silencing by PCNA and CDC45 mutations required the origin recognition complex binding site of the HMR-E silencer. Several models for the precise role of these replication proteins in silencing are discussed. ..
  32. Maloisel L, Fabre F, Gangloff S. DNA polymerase delta is preferentially recruited during homologous recombination to promote heteroduplex DNA extension. Mol Cell Biol. 2008;28:1373-82 pubmed
    ..Our results argue strongly for the preferential recruitment of Poldelta during HR. ..
  33. Li Y, Pursell Z, Linn S. Identification and cloning of two histone fold motif-containing subunits of HeLa DNA polymerase epsilon. J Biol Chem. 2000;275:23247-52 pubmed
    ..p17 together with p12, but not p17 or p12 alone, interact with both p261 and p59 subunits of HeLa pol epsilon. The genes for p17 and p12 can be assigned to chromosome locations 9q33 and 2p12, respectively. ..
  34. Dua R, Levy D, Li C, Snow P, Campbell J. In vivo reconstitution of Saccharomyces cerevisiae DNA polymerase epsilon in insect cells. Purification and characterization. J Biol Chem. 2002;277:7889-96 pubmed
    ..Mutations of the conserved cysteines in the putative zinc finger domain reduced zinc binding, indicating that cysteine ligands are directly involved in binding zinc. ..
  35. Sabouri N, Johansson E. Translesion synthesis of abasic sites by yeast DNA polymerase epsilon. J Biol Chem. 2009;284:31555-63 pubmed publisher
    ..This characteristic may allow other pathways to rescue leading strand synthesis when stalled at an abasic site. ..
  36. Fukui T, Yamauchi K, Muroya T, Akiyama M, Maki H, Sugino A, et al. Distinct roles of DNA polymerases delta and epsilon at the replication fork in Xenopus egg extracts. Genes Cells. 2004;9:179-91 pubmed
    ..Therefore, our data strongly suggest the possibilities that Poldelta is essential for lagging strand synthesis and that this function of Poldelta cannot be substituted for by Polepsilon. ..
  37. Wu X, Guo D, Yuan F, Wang Z. Accessibility of DNA polymerases to repair synthesis during nucleotide excision repair in yeast cell-free extracts. Nucleic Acids Res. 2001;29:3123-30 pubmed
    ..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. ..
  38. Thiriet C, Hayes J. Replication-independent core histone dynamics at transcriptionally active loci in vivo. Genes Dev. 2005;19:677-82 pubmed
  39. Feng W, D URSO G. Schizosaccharomyces pombe cells lacking the amino-terminal catalytic domains of DNA polymerase epsilon are viable but require the DNA damage checkpoint control. Mol Cell Biol. 2001;21:4495-504 pubmed
    ..This unique and essential function of the C terminus is preserved in the absence of the N-terminal catalytic domains, suggesting that the C terminus can interact with and recruit other DNA polymerases to the site of initiation. ..
  40. Rosonina E, Kaneko S, Manley J. Terminating the transcript: breaking up is hard to do. Genes Dev. 2006;20:1050-6 pubmed
  41. Chilkova O, Stenlund P, Isoz I, Stith C, Grabowski P, Lundström E, et al. The eukaryotic leading and lagging strand DNA polymerases are loaded onto primer-ends via separate mechanisms but have comparable processivity in the presence of PCNA. Nucleic Acids Res. 2007;35:6588-97 pubmed
    ..We conclude that Pol epsilon and Pol delta exhibit comparable processivity, but are loaded on the primer-end via different mechanisms. ..
  42. Jaszczur M, Rudzka J, Kraszewska J, Flis K, Polaczek P, Campbell J, et al. Defective interaction between Pol2p and Dpb2p, subunits of DNA polymerase epsilon, contributes to a mutator phenotype in Saccharomyces cerevisiae. Mutat Res. 2009;669:27-35 pubmed publisher
    ..We propose that structural integrity of the Pol epsilon holoenzyme is essential for genetic stability in S. cerevisiae cells. ..
  43. Bitoun E, Oliver P, Davies K. The mixed-lineage leukemia fusion partner AF4 stimulates RNA polymerase II transcriptional elongation and mediates coordinated chromatin remodeling. Hum Mol Genet. 2007;16:92-106 pubmed
    ..Since these activities likely extend to the entire ALF protein family, this study also significantly inputs our understanding of the molecular basis of FRAXE mental retardation syndrome in which FMR2 expression is silenced. ..
  44. Shikata K, Sasa Masuda T, Okuno Y, Waga S, Sugino A. The DNA polymerase activity of Pol epsilon holoenzyme is required for rapid and efficient chromosomal DNA replication in Xenopus egg extracts. BMC Biochem. 2006;7:21 pubmed
    ..These are the first biochemical data to show the DNA polymerase activity of Pol epsilon holoenzyme is essential for chromosomal DNA replication in higher eukaryotes, unlike in yeasts. ..
  45. Holmes A, Haber J. Double-strand break repair in yeast requires both leading and lagging strand DNA polymerases. Cell. 1999;96:415-24 pubmed
    ..Replication is terminated by capture of the second end of the DSB. ..
  46. Korona D, Lecompte K, Pursell Z. The high fidelity and unique error signature of human DNA polymerase epsilon. Nucleic Acids Res. 2011;39:1763-73 pubmed publisher
    ..The base pair substitution specificity and high fidelity for frameshift errors observed for human Pol ? are distinct from the errors made by human Pol ?. ..
  47. Dua R, Levy D, Campbell J. Role of the putative zinc finger domain of Saccharomyces cerevisiae DNA polymerase epsilon in DNA replication and the S/M checkpoint pathway. J Biol Chem. 1998;273:30046-55 pubmed
    ..The POL2 C terminus is sufficient for interaction with DPB2, the essential and phylogenetically conserved subunit of pol epsilon, but not for interaction with DPB3. Neither Dpb3p nor Dpb2p homodimerizes in the two-hybrid assay. ..
  48. McCulloch S, Kokoska R, Chilkova O, Welch C, Johansson E, Burgers P, et al. Enzymatic switching for efficient and accurate translesion DNA replication. Nucleic Acids Res. 2004;32:4665-75 pubmed
  49. Watt D, Johansson E, Burgers P, Kunkel T. Replication of ribonucleotide-containing DNA templates by yeast replicative polymerases. DNA Repair (Amst). 2011;10:897-902 pubmed publisher
    ..Overall, ribonucleotide bypass efficiencies are comparable to, and usually exceed, those for the common oxidative stress-induced lesion 8-oxo-guanine. ..
  50. Frisch R, Su Y, Thornton P, Gibson J, Rosenberg S, Hastings P. Separate DNA Pol II- and Pol IV-dependent pathways of stress-induced mutation during double-strand-break repair in Escherichia coli are controlled by RpoS. J Bacteriol. 2010;192:4694-700 pubmed publisher
    ..The results identify a second DNA polymerase contributing to stress-induced mutagenesis and show that RpoS promotes mutagenesis by more than the simple upregulation of dinB. ..
  51. Fijalkowska I, Dunn R, Schaaper R. Genetic requirements and mutational specificity of the Escherichia coli SOS mutator activity. J Bacteriol. 1997;179:7435-45 pubmed
    ..The modified complex forces extension of the mismatch largely at the exclusion of proofreading and polymerase dissociation pathways. SOS mutagenesis targeted at replication-blocking DNA lesions likely proceeds in the same manner. ..
  52. Williams J, Clausen A, Nick McElhinny S, Watts B, Johansson E, Kunkel T. Proofreading of ribonucleotides inserted into DNA by yeast DNA polymerase É›. DNA Repair (Amst). 2012;11:649-56 pubmed publisher
    ..Collectively, the results indicate that although proofreading of an 'incorrect' sugar is less efficient than is proofreading of an incorrect base, Pol É› does proofread newly inserted rNMPs to enhance genome stability. ..