dna polymerase iii

Summary

Summary: A DNA-dependent DNA polymerase characterized in E. coli and other lower organisms but may be present in higher organisms. Use also for a more complex form of DNA polymerase III designated as DNA polymerase III* or pol III* which is 15 times more active biologically than DNA polymerase I in the synthesis of DNA. This polymerase has both 3'-5' and 5'-3' exonuclease activities, is inhibited by sulfhydryl reagents, and has the same template-primer dependence as pol II. EC 2.7.7.7.

Top Publications

  1. Kongsuwan K, Josh P, Picault M, Wijffels G, Dalrymple B. The plasmid RK2 replication initiator protein (TrfA) binds to the sliding clamp beta subunit of DNA polymerase III: implication for the toxicity of a peptide derived from the amino-terminal portion of 33-kilodalton TrfA. J Bacteriol. 2006;188:5501-9 pubmed
  2. Lamers M, Georgescu R, Lee S, O Donnell M, Kuriyan J. Crystal structure of the catalytic alpha subunit of E. coli replicative DNA polymerase III. Cell. 2006;126:881-92 pubmed
    ..The structure also suggests a model for interaction of Pol III with the sliding clamp and DNA. ..
  3. Sanders G, Dallmann H, McHenry C. Reconstitution of the B. subtilis replisome with 13 proteins including two distinct replicases. Mol Cell. 2010;37:273-81 pubmed publisher
    ..Consistent with the in vivo requirement for two DNA polymerase III replicases for B...
  4. Acharya N, Johnson R, Pages V, Prakash L, Prakash S. Yeast Rev1 protein promotes complex formation of DNA polymerase zeta with Pol32 subunit of DNA polymerase delta. Proc Natl Acad Sci U S A. 2009;106:9631-6 pubmed publisher
    ..We discuss evidence for the biological significance of Rev1 binding to Pol32 for Pol zeta function in TLS and suggest a structural role for Rev1 in modulating the binding of Pol zeta with Pol32 in Pol delta stalled at a lesion site. ..
  5. Guiles J, Sun X, Critchley I, Ochsner U, Tregay M, Stone K, et al. Quinazolin-2-ylamino-quinazolin-4-ols as novel non-nucleoside inhibitors of bacterial DNA polymerase III. Bioorg Med Chem Lett. 2009;19:800-2 pubmed publisher
    ..screening led to the discovery of a novel series of quinazolin-2-ylamino-quinazolin-4-ols as a new class of DNA polymerase III inhibitors. The inhibition of chromosomal DNA replication results in bacterial cell death...
  6. Jergic S, Ozawa K, Williams N, Su X, Scott D, Hamdan S, et al. The unstructured C-terminus of the tau subunit of Escherichia coli DNA polymerase III holoenzyme is the site of interaction with the alpha subunit. Nucleic Acids Res. 2007;35:2813-24 pubmed
    The tau subunit of Escherichia coli DNA polymerase III holoenzyme interacts with the alpha subunit through its C-terminal Domain V, tau(C)16...
  7. Wu P, Ozawa K, Jergic S, Su X, Dixon N, Otting G. Amino-acid type identification in 15N-HSQC spectra by combinatorial selective 15N-labelling. J Biomol NMR. 2006;34:13-21 pubmed
    ..explored with two different constructs of the C-terminal domain V of the tau subunit of the Escherichia coli DNA polymerase III holoenzyme, tauC16 and tauC14...
  8. Wang L, Xu X, Kumar R, Maiti B, Liu C, Ivanov I, et al. Probing DNA clamps with single-molecule force spectroscopy. Nucleic Acids Res. 2013;41:7804-14 pubmed publisher
    ..cerevisiae and E. coli clamps. These studies provide a vivid picture of the mechanics and energy landscape of clamp opening and reveal how the prokaryotic and eukaryotic clamps function through different mechanisms. ..
  9. Wang Y, Zhang Q, Chen H, Li X, Mai W, Chen K, et al. P50, the small subunit of DNA polymerase delta, is required for mediation of the interaction of polymerase delta subassemblies with PCNA. PLoS ONE. 2011;6:e27092 pubmed publisher
    ..P50 is required for mediation of the interaction between pol ? subassemblies and PCNA homotrimer. Thus, pol ? interacts with PCNA via its four subunits. ..

More Information

Publications61

  1. Yeeles J, Marians K. The Escherichia coli replisome is inherently DNA damage tolerant. Science. 2011;334:235-8 pubmed publisher
    ..These observations reveal that the replisome can tolerate leading-strand template lesions without dissociating by synthesizing the leading strand discontinuously. ..
  2. McHenry C. Breaking the rules: bacteria that use several DNA polymerase IIIs. EMBO Rep. 2011;12:408-14 pubmed publisher
    ..coli. A complete understanding of complex bacterial replicases will allow the simultaneous biochemical screening of all their components and, thus, the identification of new antibacterial compounds. ..
  3. Baranovskiy A, Babayeva N, Liston V, Rogozin I, Koonin E, Pavlov Y, et al. X-ray structure of the complex of regulatory subunits of human DNA polymerase delta. Cell Cycle. 2008;7:3026-36 pubmed
  4. Baranovskiy A, Babayeva N, Pavlov Y, Tahirov T. Crystallization and preliminary crystallographic analysis of the complex of the second and third regulatory subunits of human Pol delta. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008;64:822-4 pubmed publisher
    ..13, b = 248.54, c = 103.46 A, beta = 106.94 degrees and diffracted to a resolution of 3 A. Four molecules of p50-p66(N) in an asymmetric unit corresponded to a crystal solvent content of 72.2%. ..
  5. Selak N, Bachrati C, Shevelev I, Dietschy T, van Loon B, Jacob A, et al. The Bloom's syndrome helicase (BLM) interacts physically and functionally with p12, the smallest subunit of human DNA polymerase delta. Nucleic Acids Res. 2008;36:5166-79 pubmed publisher
    ..Finally, our data also define a novel role for the poorly characterized p12 subunit of hPOL delta. ..
  6. Arezi B, Hogrefe H. Escherichia coli DNA polymerase III epsilon subunit increases Moloney murine leukemia virus reverse transcriptase fidelity and accuracy of RT-PCR procedures. Anal Biochem. 2007;360:84-91 pubmed
    ..number of 3'-5' exonucleases were found to lower the error rate of MMLV RT, including p53, Escherichia coli DNA polymerase III epsilon subunit, and the proofreading activities associated with T4, varphi29, and E...
  7. Li F, Liu Q, Chen Y, Yu Z, Zhang Z, Zhou Y, et al. Escherichia coli mismatch repair protein MutL interacts with the clamp loader subunits of DNA polymerase III. Mutat Res. 2008;637:101-10 pubmed
    ..hypothesized that DNA mismatch repair (MMR) is coupled with DNA replication; however, the involvement of DNA polymerase III subunits in bacterial DNA MMR has not been clearly elucidated...
  8. Titok M, Suski C, Dalmais B, Ehrlich S, Janni re L. The replicative polymerases PolC and DnaE are required for theta replication of the Bacillus subtilis plasmid pBS72. Microbiology. 2006;152:1471-8 pubmed publisher
    ..subtilis and presumably in other bacteria encoding PolC and DnaE...
  9. Keniry M, Park A, Owen E, Hamdan S, Pintacuda G, Otting G, et al. Structure of the theta subunit of Escherichia coli DNA polymerase III in complex with the epsilon subunit. J Bacteriol. 2006;188:4464-73 pubmed
    The catalytic core of Escherichia coli DNA polymerase III contains three tightly associated subunits, the alpha, epsilon, and theta subunits. The theta subunit is the smallest and least understood subunit...
  10. Daee D, Mertz T, Shcherbakova P. A cancer-associated DNA polymerase delta variant modeled in yeast causes a catastrophic increase in genomic instability. Proc Natl Acad Sci U S A. 2010;107:157-62 pubmed publisher
    ..These results suggest that the highly error-prone Poldelta-R689W could contribute to cancer initiation and/or progression in humans. ..
  11. Smith C, Lam A, Symington L. Aberrant double-strand break repair resulting in half crossovers in mutants defective for Rad51 or the DNA polymerase delta complex. Mol Cell Biol. 2009;29:1432-41 pubmed publisher
    ..Thus, the BIR defect observed for rad51 mutants is due to strand invasion failure, whereas the Pol delta complex mutants are proficient for strand invasion but unable to complete extensive tracts of recombination-initiated DNA synthesis...
  12. Su X, Jergic S, Keniry M, Dixon N, Otting G. Solution structure of Domains IVa and V of the tau subunit of Escherichia coli DNA polymerase III and interaction with the alpha subunit. Nucleic Acids Res. 2007;35:2825-32 pubmed
    The solution structure of the C-terminal Domain V of the tau subunit of E. coli DNA polymerase III was determined by nuclear magnetic resonance (NMR) spectroscopy. The fold is unique to tau subunits...
  13. Johnson R, Prakash L, Prakash S. Pol31 and Pol32 subunits of yeast DNA polymerase ? are also essential subunits of DNA polymerase ?. Proc Natl Acad Sci U S A. 2012;109:12455-60 pubmed publisher
    ..To distinguish the four-subunit complex from the two-subunit Pol?, we designate the four-subunit enzyme "Pol?-d," where "-d" denotes the Pol31/Pol32 subunits of Pol?. ..
  14. Yamada M, Shimizu M, Katafuchi A, Gruz P, Fujii S, Usui Y, et al. Escherichia coli DNA polymerase III is responsible for the high level of spontaneous mutations in mutT strains. Mol Microbiol. 2012;86:1364-75 pubmed publisher
    ..coli mutT compared with the mammalian counterparts lacking the 8-oxo-dGTP hydrolysing activities. ..
  15. Ter Brake O, t Hooft K, Liu Y, Centlivre M, von Eije K, Berkhout B. Lentiviral vector design for multiple shRNA expression and durable HIV-1 inhibition. Mol Ther. 2008;16:557-64 pubmed publisher
    ..Moreover, whereas HIV-1 could escape from a single shRNA, we now show that HIV-1 escape can be prevented when four shRNAs are simultaneously expressed in a cell. ..
  16. Ozawa K, Horan N, Robinson A, Yagi H, Hill F, Jergic S, et al. Proofreading exonuclease on a tether: the complex between the E. coli DNA polymerase III subunits ?, epsilon, ? and ? reveals a highly flexible arrangement of the proofreading domain. Nucleic Acids Res. 2013;41:5354-67 pubmed publisher
    ..Structural models of the ???:?2 replicase complex with primer-template DNA combine all available structural data. ..
  17. 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. ..
  18. Ruike T, Takeuchi R, Takata K, Oshige M, Kasai N, Shimanouchi K, et al. Characterization of a second proliferating cell nuclear antigen (PCNA2) from Drosophila melanogaster. FEBS J. 2006;273:5062-73 pubmed
    ..Our observations suggest that DmPCNA2 may function as an independent sliding clamp of DmPCNA1 when DNA repair occurs. ..
  19. Dohrmann P, Manhart C, Downey C, McHenry C. The rate of polymerase release upon filling the gap between Okazaki fragments is inadequate to support cycling during lagging strand synthesis. J Mol Biol. 2011;414:15-27 pubmed publisher
    ..Probing with surface plasmon resonance, DNA polymerase III holoenzyme initiation complexes were formed on an immobilized gapped template...
  20. Abdulovic A, Hile S, Kunkel T, Eckert K. The in vitro fidelity of yeast DNA polymerase ? and polymerase ? holoenzymes during dinucleotide microsatellite DNA synthesis. DNA Repair (Amst). 2011;10:497-505 pubmed publisher
  21. Gui W, Lin S, Chen Y, Zhang X, Bi L, Jiang T. Crystal structure of DNA polymerase III ? sliding clamp from Mycobacterium tuberculosis. Biochem Biophys Res Commun. 2011;405:272-7 pubmed publisher
    The sliding clamp is a key component of DNA polymerase III (Pol III) required for genome replication. It is known to function with diverse DNA repair proteins and cell cycle-control proteins, making it a potential drug target...
  22. Lockless S, Muir T. Traceless protein splicing utilizing evolved split inteins. Proc Natl Acad Sci U S A. 2009;106:10999-1004 pubmed publisher
    ..Mutations within these evolved inteins occur at sites distant from the active site. We present a hypothesis that a network of conserved coevolving amino acids in inteins mediates these long-range effects. ..
  23. Oeemig J, Aranko A, Djupsjöbacka J, Heinämäki K, Iwai H. Solution structure of DnaE intein from Nostoc punctiforme: structural basis for the design of a new split intein suitable for site-specific chemical modification. FEBS Lett. 2009;583:1451-6 pubmed publisher
    ..In vivo and in vitro protein ligation of model proteins by the newly designed split intein were demonstrated. ..
  24. Scouten Ponticelli S, Duzen J, Sutton M. Contributions of the individual hydrophobic clefts of the Escherichia coli beta sliding clamp to clamp loading, DNA replication and clamp recycling. Nucleic Acids Res. 2009;37:2796-809 pubmed publisher
  25. 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
    ..coli DNA polymerases. The dnaX gene encodes the tau subunit of DNA polymerase III (Pol III) holoenzyme, the enzyme responsible for replication of the bacterial chromosome...
  26. Uchimura A, Hidaka Y, Hirabayashi T, Hirabayashi M, Yagi T. DNA polymerase delta is required for early mammalian embryogenesis. PLoS ONE. 2009;4:e4184 pubmed publisher
  27. Aranko A, Züger S, Buchinger E, Iwai H. In vivo and in vitro protein ligation by naturally occurring and engineered split DnaE inteins. PLoS ONE. 2009;4:e5185 pubmed publisher
  28. Fang J, Engen J, Beuning P. Escherichia coli processivity clamp ? from DNA polymerase III is dynamic in solution. Biochemistry. 2011;50:5958-68 pubmed publisher
    Escherichia coli DNA polymerase III is a highly processive replicase because of the presence of the ? clamp protein that tethers DNA polymerases to DNA...
  29. Herr A, Ogawa M, Lawrence N, Williams L, Eggington J, Singh M, et al. Mutator suppression and escape from replication error-induced extinction in yeast. PLoS Genet. 2011;7:e1002282 pubmed publisher
    ..Our studies reveal the transient nature of eukaryotic mutators and show that mutator phenotypes are readily suppressed by genetic adaptation. This has implications for the role of mutator phenotypes in cancer. ..
  30. Acharya N, Klassen R, Johnson R, Prakash L, Prakash S. PCNA binding domains in all three subunits of yeast DNA polymerase ? modulate its function in DNA replication. Proc Natl Acad Sci U S A. 2011;108:17927-32 pubmed publisher
    ..We consider the implications of these observations for Pol?'s role in DNA replication. ..
  31. Stefan A, Tabler M, Hochkoeppler A. Efficient silencing of the gene coding for the epsilon subunit of DNA polymerase III in Escherichia coli is triggered by antisense RNAs featuring stability in vivo. FEMS Microbiol Lett. 2007;270:277-83 pubmed
    The Escherichia coli gene dnaQ coding for the epsilon subunit of DNA polymerase III was suppressed in vivo via antisense RNAs...
  32. Georgescu R, Kurth I, O Donnell M. Single-molecule studies reveal the function of a third polymerase in the replisome. Nat Struct Mol Biol. 2011;19:113-6 pubmed publisher
    ..Second, tripolymerase replisomes are much more processive than dipolymerase replisomes. These features account for the unexpected three-polymerase-structure of bacterial replisomes. ..
  33. Kamath Loeb A, Shen J, Schmitt M, Loeb L. The Werner syndrome exonuclease facilitates DNA degradation and high fidelity DNA polymerization by human DNA polymerase ?. J Biol Chem. 2012;287:12480-90 pubmed publisher
    ..Together, our data highlight the importance of WRN exonuclease activity and its cooperativity with Pol ? in preserving genome stability, which is compromised by the loss of WRN in Werner syndrome. ..
  34. Ghosal G, Leung J, Nair B, Fong K, Chen J. Proliferating cell nuclear antigen (PCNA)-binding protein C1orf124 is a regulator of translesion synthesis. J Biol Chem. 2012;287:34225-33 pubmed publisher
    ..Thus, C1orf124 acts at multiple steps in TLS, stabilizes RAD18 and ubiquitinated PCNA at damage sites, and facilitates the switch from replicative to TLS polymerase to bypass DNA lesion. ..
  35. Yanagihara F, Yoshida S, Sugaya Y, Maki H. The dnaE173 mutator mutation confers on the alpha subunit of Escherichia coli DNA polymerase III a capacity for highly processive DNA synthesis and stable binding to primer/template DNA. Genes Genet Syst. 2007;82:273-80 pubmed
    The strong mutator mutation dnaE173 which causes an amino-acid substitution in the alpha subunit of DNA polymerase III is unique in its ability to induce sequence-substitution mutations...
  36. 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. ..
  37. Stillman B. DNA polymerases at the replication fork in eukaryotes. Mol Cell. 2008;30:259-60 pubmed publisher
    ..The Kunkel laboratory has recently assigned polymerase (Pol) epsilon as the leading strand polymerase. In a recent issue of Molecular Cell, they now assign Pol delta as the lagging strand polymerase. ..
  38. Lemoine F, Degtyareva N, Kokoska R, Petes T. Reduced levels of DNA polymerase delta induce chromosome fragile site instability in yeast. Mol Cell Biol. 2008;28:5359-68 pubmed publisher
    ..These findings demonstrate that a change in the stoichiometry of replicative DNA polymerases results in recombinogenic DNA lesions, presumably double-strand DNA breaks. ..
  39. Shah S, Opresko P, Meng X, Lee M, Eckert K. DNA structure and the Werner protein modulate human DNA polymerase delta-dependent replication dynamics within the common fragile site FRA16D. Nucleic Acids Res. 2010;38:1149-62 pubmed publisher
    ..Our data support a model whereby CFS expression during cellular stress is due to a combination of factors--density of specific DNA secondary-structures within a genomic region and asymmetric rates of strand synthesis. ..
  40. Silva M, Nevin P, Ronayne E, Beuning P. Selective disruption of the DNA polymerase III ?-? complex by the umuD gene products. Nucleic Acids Res. 2012;40:5511-22 pubmed publisher
    b>DNA polymerase III (DNA pol III) efficiently replicates the Escherichia coli genome, but it cannot bypass DNA damage...
  41. Schmitz C, Stanton Cook M, Su X, Otting G, Huber T. Numbat: an interactive software tool for fitting Deltachi-tensors to molecular coordinates using pseudocontact shifts. J Biomol NMR. 2008;41:179-89 pubmed publisher
    ..Use of the program for Linux and Windows operating systems is illustrated by building a model of the complex between the E. coli DNA polymerase III subunits epsilon186 and theta using PCS.
  42. Marceau A, Bahng S, Massoni S, George N, Sandler S, Marians K, et al. Structure of the SSB-DNA polymerase III interface and its role in DNA replication. EMBO J. 2011;30:4236-47 pubmed publisher
    ..In Escherichia coli, SSB's association with the ? subunit of the DNA polymerase III holoenzyme has been proposed to confer stability to the replisome and to aid delivery of primers to the ..
  43. Zhou Y, Chen H, Li X, Wang Y, Chen K, Zhang S, et al. Production of recombinant human DNA polymerase delta in a Bombyx mori bioreactor. PLoS ONE. 2011;6:e22224 pubmed publisher
  44. 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. ..
  45. Rossi M, Pike J, Wang W, Burgers P, Campbell J, Bambara R. Pif1 helicase directs eukaryotic Okazaki fragments toward the two-nuclease cleavage pathway for primer removal. J Biol Chem. 2008;283:27483-93 pubmed publisher
    ..Therefore, Pif1 directs long flaps toward the two-nuclease pathway, requiring Dna2 cleavage for primer removal. ..
  46. Schmitz C, John M, Park A, Dixon N, Otting G, Pintacuda G, et al. Efficient chi-tensor determination and NH assignment of paramagnetic proteins. J Biomol NMR. 2006;35:79-87 pubmed
    ..Examples are shown for the 185-residue N-terminal domain of the subunit epsilon from E. coli DNA polymerase III in complex with the subunit theta and La3+ in its diamagnetic and Dy3+, Tb3+, and Er3+ in its paramagnetic ..
  47. Meng X, Zhou Y, Zhang S, Lee E, Frick D, Lee M. DNA damage alters DNA polymerase delta to a form that exhibits increased discrimination against modified template bases and mismatched primers. Nucleic Acids Res. 2009;37:647-57 pubmed publisher
  48. Zheng L, Shen B. Okazaki fragment maturation: nucleases take centre stage. J Mol Cell Biol. 2011;3:23-30 pubmed publisher
    ..On the other hand, mutations that impair editing out of polymerase ? incorporation errors result in cancer displaying a strong mutator phenotype. ..
  49. Meng X, Zhou Y, Lee E, Lee M, Frick D. The p12 subunit of human polymerase delta modulates the rate and fidelity of DNA synthesis. Biochemistry. 2010;49:3545-54 pubmed publisher
    ..The loss of p12, which occurs in cells upon exposure to DNA-damaging agents, converts Pol delta to a form that has an increased capacity for proofreading. ..
  50. Beuning P, Simon S, Zemla A, Barsky D, Walker G. A non-cleavable UmuD variant that acts as a UmuD' mimic. J Biol Chem. 2006;281:9633-40 pubmed
  51. Dunlop M, Dobbins S, Farrington S, Jones A, Palles C, Whiffin N, et al. Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk. Nat Genet. 2012;44:770-6 pubmed publisher
    ..2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC. ..
  52. Zhao X, Zhang Z, Yan J, Yu J. GC content variability of eubacteria is governed by the pol III alpha subunit. Biochem Biophys Res Commun. 2007;356:20-5 pubmed
    ..The place to look for is what actually catalyzes the synthesis of DNA, where DNA polymerase III is at the center stage, particularly one of its 10 subunits--the alpha subunit...