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Eukaryotic DNA Replicases

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Molecular Life Sciences

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Synopsis

The current model of the eukaryotic DNA replication fork includes three replicative DNA polymerases, polymerase α/primase complex (Pol α), polymerase δ (Pol δ), and polymerase ε (Pol ε). The primase synthesizes 8–12 nucleotide RNA primers that are extended by the DNA polymerization activity of Pol α into 30–35 nucleotide RNA-DNA primers. Replication factor C (RFC) opens the polymerase clamp-like processivity factor, proliferating cell nuclear antigen (PCNA), and loads it onto the primer-template. Pol δ utilizes PCNA to mediate highly processive DNA synthesis, while Pol ε has intrinsic high processivity that is modestly stimulated by PCNA. Pol ε replicates the leading strand and Pol δ replicates the lagging strand in a division of labor that is not strict. The three polymerases are comprised of multiple subunits and share unifying features in their large catalytic and B subunits. The remaining subunits are evolutionarily not related and perform diverse functions. The catalytic...

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References

  • Acharya N, Johnson RE, Pages V, Prakash L, Prakash S (2009) Yeast Rev1 protein promotes complex formation of DNA polymerase zeta with Pol32 subunit of DNA polymerase delta. Proc Natl Acad Sci U S A 106(24):9631–9636

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Agarkar VB, Babayeva ND, Pavlov YI, Tahirov TH (2011) Crystal structure of the C-terminal domain of human DNA primase large subunit: implications for the mechanism of the primase-polymerase alpha switch. Cell Cycle 10(6):926–931

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Asturias FJ, Cheung IK, Sabouri N, Chilkova O, Wepplo D, Johansson E (2006) Structure of Saccharomyces cerevisiae DNA polymerase epsilon by cryo-electron microscopy. Nat Struct Mol Biol 13(1):35–43

    Article  CAS  PubMed  Google Scholar 

  • Augustin MA, Huber R, Kaiser JT (2001) Crystal structure of a DNA-dependent RNA polymerase (DNA primase). Nat Struct Biol 8(1):57–61

    Article  CAS  PubMed  Google Scholar 

  • Baranovskiy AG, Babayeva ND, Liston VG, Rogozin IB, Koonin EV, Pavlov YI, Vassylyev DG, Tahirov TH (2008) X-ray structure of the complex of regulatory subunits of human DNA polymerase delta. Cell Cycle 7(19):3026–3036

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bebenek K, Kunkel TA (2004) Functions of DNA polymerases. Adv Protein Chem 69:137–165

    Article  CAS  PubMed  Google Scholar 

  • Bowman GD, O’Donnell M, Kuriyan J (2004) Structural analysis of a eukaryotic sliding DNA clamp-clamp loader complex. Nature 429(6993):724–730

    Article  CAS  PubMed  Google Scholar 

  • Franklin MC, Wang J, Steitz TA (2001) Structure of the replicating complex of a pol alpha family DNA polymerase. Cell 105(5):657–667

    Article  CAS  PubMed  Google Scholar 

  • Frick DN, Richardson CC (2001) DNA primases. Annu Rev Biochem 70:39–80

    Article  CAS  PubMed  Google Scholar 

  • Garg P, Burgers PM (2005) DNA polymerases that propagate the eukaryotic DNA replication fork. Crit Rev Biochem Mol Biol 40(2):115–128

    Article  CAS  PubMed  Google Scholar 

  • Hamdan SM, Richardson CC (2009) Motors, switches, and contacts in the replisome. Annu Rev Biochem 78:205–243

    Article  CAS  PubMed  Google Scholar 

  • Hamdan SM, van Oijen AM (2010) Timing, coordination, and rhythm: acrobatics at the DNA replication fork. J Biol Chem 285(25):18979–18983

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hogg M, Johansson E (2012) DNA polymerase epsilon. Subcell Biochem 62:237–257

    Article  CAS  PubMed  Google Scholar 

  • Hogg M, Osterman P, Bylund GO, Ganai RA, Lundstrom EB, Sauer-Eriksson AE, Johansson E (2014) Structural basis for processive DNA synthesis by yeast DNA polymerase varepsilon. Nat Struct Mol Biol 21(1):49–55

    Article  CAS  PubMed  Google Scholar 

  • Ito N, Nureki O, Shirouzu M, Yokoyama S, Hanaoka F (2003) Crystal structure of the Pyrococcus horikoshii DNA primase-UTP complex: implications for the mechanism of primer synthesis. Genes Cells 8(12):913–923

    Article  CAS  PubMed  Google Scholar 

  • Jain R, Hammel M, Johnson RE, Prakash L, Prakash S, Aggarwal AK (2009) Structural insights into yeast DNA polymerase delta by small angle X-ray scattering. J Mol Biol 394(3):377–382

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Jain R, Rajashankar KR, Buku A, Johnson RE, Prakash L, Prakash S, Aggarwal AK (2014) Crystal structure of yeast DNA polymerase epsilon catalytic domain. PLoS One 9(4):e94835

    Article  PubMed Central  PubMed  Google Scholar 

  • Johansson E, Macneill SA (2010) The eukaryotic replicative DNA polymerases take shape. Trends Biochem Sci 35(6):339–347

    Article  CAS  PubMed  Google Scholar 

  • Johnson A, O’Donnell M (2005) Cellular DNA replicases: components and dynamics at the replication fork. Annu Rev Biochem 74:283–315

    Article  CAS  PubMed  Google Scholar 

  • Kilkenny ML, Longo MA, Perera RL, Pellegrini L (2013) Structures of human primase reveal design of nucleotide elongation site and mode of Pol alpha tethering. Proc Natl Acad Sci U S A 110(40):15961–15966

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Klinge S, Hirst J, Maman JD, Krude T, Pellegrini L (2007) An iron-sulfur domain of the eukaryotic primase is essential for RNA primer synthesis. Nat Struct Mol Biol 14(9):875–877

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Klinge S, Nunez-Ramirez R, Llorca O, Pellegrini L (2009) 3D architecture of DNA Pol alpha reveals the functional core of multi-subunit replicative polymerases. EMBO J 28(13):1978–1987

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Krishna TS, Kong XP, Gary S, Burgers PM, Kuriyan J (1994) Crystal structure of the eukaryotic DNA polymerase processivity factor PCNA. Cell 79(7):1233–1243

    Article  CAS  PubMed  Google Scholar 

  • Kuchta RD, Reid B, Chang LM (1990) DNA primase. Processivity and the primase to polymerase alpha activity switch. J Biol Chem 265(27):16158–16165

    CAS  PubMed  Google Scholar 

  • Lao-Sirieix SH, Nookala RK, Roversi P, Bell SD, Pellegrini L (2005) Structure of the heterodimeric core primase. Nat Struct Mol Biol 12(12):1137–1144

    Article  CAS  PubMed  Google Scholar 

  • McHenry CS (2011) DNA replicases from a bacterial perspective. Annu Rev Biochem 80:403–436

    Article  CAS  PubMed  Google Scholar 

  • Netz DJ, Stith CM, Stumpfig M, Kopf G, Vogel D, Genau HM, Stodola JL, Lill R, Burgers PM, Pierik AJ (2012) Eukaryotic DNA polymerases require an iron-sulfur cluster for the formation of active complexes. Nat Chem Biol 8(1):125–132

    Article  CAS  Google Scholar 

  • Nunez-Ramirez R, Klinge S, Sauguet L, Melero R, Recuero-Checa MA, Kilkenny M, Perera RL, Garcia-Alvarez B, Hall RJ, Nogales E, Pellegrini L, Llorca O (2011) Flexible tethering of primase and DNA Pol alpha in the eukaryotic primosome. Nucleic Acids Res 39(18):8187–8199

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nuutinen T, Tossavainen H, Fredriksson K, Pirila P, Permi P, Pospiech H, Syvaoja JE (2008) 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 36(15):5102–5110

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pavlov YI, Shcherbakova PV (2010) DNA polymerases at the eukaryotic fork-20 years later. Mutat Res 685(1–2):45–53

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pellegrini L (2012) The Pol alpha-primase complex. Subcell Biochem 62:157–169

    Article  CAS  PubMed  Google Scholar 

  • Perera RL, Torella R, Klinge S, Kilkenny ML, Maman JD, Pellegrini L (2013) Mechanism for priming DNA synthesis by yeast DNA polymerase alpha. Elife 2:e00482

    Article  PubMed Central  PubMed  Google Scholar 

  • Sauguet L, Klinge S, Perera RL, Maman JD, Pellegrini L (2010) Shared active site architecture between the large subunit of eukaryotic primase and DNA photolyase. PLoS One 5(4):e10083

    Article  PubMed Central  PubMed  Google Scholar 

  • Swan MK, Johnson RE, Prakash L, Prakash S, Aggarwal AK (2009) Structural basis of high-fidelity DNA synthesis by yeast DNA polymerase delta. Nat Struct Mol Biol 16(9):979–986

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tahirov TH (2012) Structure and function of eukaryotic DNA polymerase delta. Subcell Biochem 62:217–236

    Article  CAS  PubMed  Google Scholar 

  • Vaithiyalingam S, Warren EM, Eichman BF, Chazin WJ (2010) Insights into eukaryotic DNA priming from the structure and functional interactions of the 4Fe-4S cluster domain of human DNA primase. Proc Natl Acad Sci U S A 107(31):13684–13689

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Biological and Environmental Sciences and Engineering, Laboratory of DNA Replication and Recombination, King Abdullah University of Science and Technology (KAUST), 23955-6900, Thuwal, Saudi Arabia

    Manal S. Zaher, Muse Oke & Samir M. Hamdan

Authors
  1. Manal S. Zaher
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  2. Muse Oke
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  3. Samir M. Hamdan
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Correspondence to Samir M. Hamdan .

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Editors and Affiliations

  1. Dept of Chemistry, University of Richmond, Richmond, Virginia, USA

    Ellis Bell

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Zaher, M.S., Oke, M., Hamdan, S.M. (2014). Eukaryotic DNA Replicases. In: Bell, E. (eds) Molecular Life Sciences. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6436-5_55-4

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  • DOI: https://doi.org/10.1007/978-1-4614-6436-5_55-4

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  • Online ISBN: 978-1-4614-6436-5

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