Synopsis
The first assignment of DNA polymerases at the eukaryotic replication fork was possible after the in vitro reconstitution of the simian virus 40 (SV40) replication system. In this system, DNA polymerase α (Pol α) provides both leading and lagging strands with RNA-DNA primers that are extended by DNA polymerase δ (Pol δ). Extrapolating the architecture of the replication fork from the SV40 model system to an actual eukaryotic cell has been challenged by the discovery of a third DNA polymerase in Saccharomyces cerevisiae, DNA polymerase ε (Pol ε). A division of labor has been proposed for the eukaryotic replication fork whereby Pol ε replicates the leading strand and Pol δ replicates the lagging strand. However, an alternative model of unequal division of labor in which Pol δ can still participate in leading-strand synthesis is plausible.
Introduction
Eukaryotic chromosomes have multiple origins of replication (ori) that are spaced apart by ~30–100 kilo bases (kb). Initiation...
This is a preview of subscription content, log in via an institution to check access.
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
Daube SS, Tomer G, Livneh Z (2000) Translesion replication by DNA polymerase delta depends on processivity accessory proteins and differs in specificity from DNA polymerase beta. Biochemistry 39(2):348–355
Dua R, Levy DL, Campbell JL (1999) Analysis of the essential functions of the C-terminal protein/protein interaction domain of Saccharomyces cerevisiae pol epsilon and its unexpected ability to support growth in the absence of the DNA polymerase domain. J Biol Chem 274(32):22283–22288
Feng W, D’Urso G (2001) 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 21(14):4495–4504
Garg P, Stith CM, Sabouri N, Johansson E, Burgers PM (2004) Idling by DNA polymerase delta maintains a ligatable nick during lagging-strand DNA replication. Genes Dev 18(22):2764–2773
Karthikeyan R, Vonarx EJ, Straffon AF, Simon M, Faye G, Kunz BA (2000) Evidence from mutational specificity studies that yeast DNA polymerases delta and epsilon replicate different DNA strands at an intracellular replication fork. J Mol Biol 299(2):405–419
Kesti T, Flick K, Keranen S, Syvaoja JE, Wittenberg C (1999) DNA polymerase epsilon catalytic domains are dispensable for DNA replication, DNA repair, and cell viability. Mol Cell 3(5):679–685
Kunkel TA, Burgers PM (2008) Dividing the workload at a eukaryotic replication fork. Trends Cell Biol 18(11):521–527
Larrea AA, Lujan SA, Nick McElhinny SA, Mieczkowski PA, Resnick MA, Gordenin DA, Kunkel TA (2010) Genome-wide model for the normal eukaryotic DNA replication fork. Proc Natl Acad Sci U S A 107(41):17674–17679
Minnick DT, Bebenek K, Osheroff WP, Turner RM Jr, Astatke M, Liu L, Kunkel TA, Joyce CM (1999) Side chains that influence fidelity at the polymerase active site of Escherichia coli DNA polymerase I (Klenow fragment). J Biol Chem 274(5):3067–3075
Miyabe I, Kunkel TA, Carr AM (2011) The major roles of DNA polymerases epsilon and delta at the eukaryotic replication fork are evolutionarily conserved. PLoS Genet 7(12):e1002407
Morrison A, Sugino A (1994) The 3′→5′ exonucleases of both DNA polymerases delta and epsilon participate in correcting errors of DNA replication in Saccharomyces cerevisiae. Mol Gen Genet 242(3):289–296
Morrison A, Araki H, Clark AB, Hamatake RK, Sugino A (1990) A third essential DNA polymerase in S. cerevisiae. Cell 62(6):1143–1151
Morrison A, Johnson AL, Johnston LH, Sugino A (1993) Pathway correcting DNA replication errors in Saccharomyces cerevisiae. EMBO J 12(4):1467–1473
Nick McElhinny SA, Gordenin DA, Stith CM, Burgers PM, Kunkel TA (2008) Division of labor at the eukaryotic replication fork. Mol Cell 30(2):137–144
Pavlov YI, Shcherbakova PV (2010) DNA polymerases at the eukaryotic fork-20 years later. Mutat Res 685(1–2):45–53
Pavlov YI, Shcherbakova PV, Kunkel TA (2001) In vivo consequences of putative active site mutations in yeast DNA polymerases alpha, epsilon, delta, and zeta. Genetics 159(1):47–64
Pavlov YI, Frahm C, Nick McElhinny SA, Niimi A, Suzuki M, Kunkel TA (2006) Evidence that errors made by DNA polymerase alpha are corrected by DNA polymerase delta. Curr Biol 16(2):202–207
Prakash S, Johnson RE, Prakash L (2005) Eukaryotic translesion synthesis DNA polymerases: specificity of structure and function. Annu Rev Biochem 74:317–353
Pursell ZF, Isoz I, Lundstrom EB, Johansson E, Kunkel TA (2007) Yeast DNA polymerase epsilon participates in leading-strand DNA replication. Science 317(5834):127–130
Shcherbakova PV, Pavlov YI (1996) 3′→5′ exonucleases of DNA polymerases epsilon and delta correct base analog induced DNA replication errors on opposite DNA strands in Saccharomyces cerevisiae. Genetics 142(3):717–726
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer Science+Business Media New York
About this entry
Cite this entry
Oke, M., Zaher, M.S., Hamdan, S.M. (2014). Division of Labor. In: Bell, E. (eds) Molecular Life Sciences. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6436-5_134-1
Download citation
DOI: https://doi.org/10.1007/978-1-4614-6436-5_134-1
Received:
Accepted:
Published:
Publisher Name: Springer, New York, NY
Online ISBN: 978-1-4614-6436-5
eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences