Genomes and Genes
Gene Symbol: POL2
Description: DNA polymerase epsilon catalytic subunit
Alias: DUN2, DNA polymerase epsilon catalytic subunit
Species: Saccharomyces cerevisiae S288c
- 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..states of the telomere gene are not stably inherited in cells either bearing a mutation in a catalytic subunit (Pol2) of replicative DNA polymerase epsilon (Pol epsilon) or lacking one of the nonessential and histone fold motif-..
- 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..The genes POL2, DPB2 and DPB3, encoding the catalytic Pol2p, the second (Dpb2p) and the third largest subunits (Dpb3p) of the ..
- Northam M, Garg P, Baitin D, Burgers P, Shcherbakova P. A novel function of DNA polymerase zeta regulated by PCNA. EMBO J. 2006;25:4316-25 pubmed
- Muramatsu S, Hirai K, Tak Y, Kamimura Y, Araki H. CDK-dependent complex formation between replication proteins Dpb11, Sld2, Pol (epsilon}, and GINS in budding yeast. Genes Dev. 2010;24:602-12 pubmed publisher..We propose that CDK regulates the initiation of DNA replication in budding yeast through formation of the pre-LC. ..
- 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..In addition to a large subunit (Pol2) harboring the polymerase and proofreading exonuclease active sites, Pol ? also has one essential subunit (Dpb2) ..
- 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. ..
- 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..An allele, pol2-C1089Y, was identified in a screen of Polepsilon mutants that in combination with an exonuclease I (exo1) mutation ..
- 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. ..
- Nick McElhinny S, Kumar D, Clark A, Watt D, Watts B, LundstrÃ¶m E, et al. Genome instability due to ribonucleotide incorporation into DNA. Nat Chem Biol. 2010;6:774-81 pubmed publisher..This hierarchy was recapitulated in vivo in yeast strains lacking RNase H2. Moreover, the pol2-M644G rnh201Î” strain progressed more slowly through S phase, had elevated dNTP pools and generated 2-5-base-..
- Williams L, Herr A, Preston B. Emergence of DNA polymerase ? antimutators that escape error-induced extinction in yeast. Genetics. 2013;193:751-70 pubmed publisher..It is unclear whether a similar synthetic lethal relationship exists between defects in Pol ? proofreading (pol2-4) and MMR...
- 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..When Msh6-dependent repair of replication errors is defective, the mutation rate of a pol2-M644F strain is 16-fold higher than that of a strain with wild-type Pol epsilon...
- Pursell Z, Isoz I, Lundström E, Johansson E, Kunkel T. Yeast DNA polymerase epsilon participates in leading-strand DNA replication. Science. 2007;317:127-30 pubmed
- Lou H, Komata M, Katou Y, Guan Z, Reis C, Budd M, et al. Mrc1 and DNA polymerase epsilon function together in linking DNA replication and the S phase checkpoint. Mol Cell. 2008;32:106-17 pubmed publisher..We report that Mrc1 interacts with Pol2, the catalytic subunit of DNA polymerase epsilon, essential for leading-strand DNA replication and for the ..
- 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. ..
- Pavlov Y, Maki S, Maki H, Kunkel T. Evidence for interplay among yeast replicative DNA polymerases alpha, delta and epsilon from studies of exonuclease and polymerase active site mutations. BMC Biol. 2004;2:11 pubmed..A pol2-Y831A mutation leading to a tyrosine to alanine change in the Pol epsilon active site does not cause growth defects ..
- Chilkova O, Jonsson B, Johansson E. The quaternary structure of DNA polymerase epsilon from Saccharomyces cerevisiae. J Biol Chem. 2003;278:14082-6 pubmedDNA polymerase epsilon (Pol epsilon) from Saccharomyces cerevisiae consists of four subunits (Pol2, Dpb2, Dpb3, and Dpb4) and is essential for chromosomal DNA replication...
- 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 pubmedIt has been proposed that C-terminal motifs of the catalytic subunit of budding yeast polymerase (pol) epsilon (POL2) couple DNA replication to the S/M checkpoint (Navas, T. A., Zheng, Z., and Elledge, S. J. (1995) Cell 80, 29-39)...
- Masumoto H, Sugino A, Araki H. Dpb11 controls the association between DNA polymerases alpha and epsilon and the autonomously replicating sequence region of budding yeast. Mol Cell Biol. 2000;20:2809-17 pubmed..This indicates that Dpb11 may also be involved in the regulation of late-origin firing. Overall, these results suggest that Dpb11 controls the association between DNA polymerases alpha and epsilon and the ARS. ..
- 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..Genetic interactions were examined among DNA polymerase epsilon (pol2-4) and delta (pol3-01) mutants defective in 3'-->5' proofreading exonuclease, mutants defective in the 5'-->3'..
- 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. ..
- 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 pubmedSaccharomyces cerevisiae POL2 encodes the catalytic subunit of DNA polymerase epsilon. This study investigates the cellular functions performed by the polymerase domain of Pol2p and its role in DNA metabolism...
- McConnell A, Gelbart M, Tsukiyama T. Histone fold protein Dls1p is required for Isw2-dependent chromatin remodeling in vivo. Mol Cell Biol. 2004;24:2605-13 pubmed..Dls1p is likely required for functions of the Isw2 complex at steps subsequent to its interaction with chromatin, since a dls1 mutation does not affect cross-linking of Isw2 with chromatin. ..
- Hamatake R, Hasegawa H, Clark A, Bebenek K, Kunkel T, Sugino A. Purification and characterization of DNA polymerase II from the yeast Saccharomyces cerevisiae. Identification of the catalytic core and a possible holoenzyme form of the enzyme. J Biol Chem. 1990;265:4072-83 pubmed
- Tackett A, Dilworth D, Davey M, O DONNELL M, Aitchison J, Rout M, et al. Proteomic and genomic characterization of chromatin complexes at a boundary. J Cell Biol. 2005;169:35-47 pubmed..We show that these complexes are important for the faithful maintenance of an established boundary, as disruption of the complexes results in specific, anomalous alterations of the silent and active epigenetic states. ..
- 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..but was reduced after thermal inactivation of the temperature-sensitive mutant Poldelta (pol3-1) or Polvarepsilon (pol2-18)...
- Morrison A, Sugino A. The 3'-->5' exonucleases of both DNA polymerases delta and epsilon participate in correcting errors of DNA replication in Saccharomyces cerevisiae. Mol Gen Genet. 1994;242:289-96 pubmed..mutator phenotypes of DNA polymerase delta and epsilon 3'-->5' exonuclease-deficient mutants, pol3-01 and pol2-4, respectively...
- Kolodner R, Marsischky G. Eukaryotic DNA mismatch repair. Curr Opin Genet Dev. 1999;9:89-96 pubmed..MMR proteins function in these processes in conjunction with components of nucleotide excision repair (NER) and, possibly, recombination. ..
- Burgers P. Eukaryotic DNA polymerases in DNA replication and DNA repair. Chromosoma. 1998;107:218-27 pubmed..The role of DNA polymerase beta in base-excision repair is well established for mammalian systems, but in yeast, DNA polymerase delta appears to fulfill that function. ..
- 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..Several of the newly isolated dpb2 alleles are strong mutators, exhibiting mutation rates equivalent to pol2 mutants defective in the 3' --> 5' proofreading exonuclease (pol2-4) or to mutants defective in mismatch repair (..
- GarcÃa RodrÃguez L, De Piccoli G, Marchesi V, Jones R, Edmondson R, Labib K. A conserved PolÏµ binding module in Ctf18-RFC is required for S-phase checkpoint activation downstream of Mec1. Nucleic Acids Res. 2015;43:8830-8 pubmed publisher..These findings indicate that the association of Ctf18-RFC with Pol Ïµ at defective replication forks is a key step in activation of the S-phase checkpoint. ..
- Sen R, Lahudkar S, Durairaj G, Bhaumik S. Functional analysis of Bre1p, an E3 ligase for histone H2B ubiquitylation, in regulation of RNA polymerase II association with active genes and transcription in vivo. J Biol Chem. 2013;288:9619-33 pubmed publisher..Similar results are also obtained at other genes. Collectively, our results implicate both the stimulatory and repressive roles of Bre1p in regulation of RNA polymerase II association with active genes (and hence transcription) in vivo. ..
- Sengupta S, van Deursen F, De Piccoli G, Labib K. Dpb2 integrates the leading-strand DNA polymerase into the eukaryotic replisome. Curr Biol. 2013;23:543-52 pubmed publisher..Second, it plays an equally important role after initiation, because it links the leading strand DNA polymerase to the Cdc45-MCM-GINS helicase within the replisome. ..
- Kadyrova L, Mertz T, Zhang Y, Northam M, Sheng Z, Lobachev K, et al. A reversible histone H3 acetylation cooperates with mismatch repair and replicative polymerases in maintaining genome stability. PLoS Genet. 2013;9:e1003899 pubmed publisher..Our results suggest that cyclic acetylation and deacetylation of chromatin contribute to replication fidelity and play important roles in the protection of nuclear DNA from diverse spontaneous mutations. ..
- Bruck I, Kaplan D. The replication initiation protein Sld2 regulates helicase assembly. J Biol Chem. 2014;289:1948-59 pubmed publisher..We also study a mutant of Sld2 that is defective in binding DNA, sld2-DNA, and find that sld2-DNA cells exhibit no GINS-Mcm2-7 interaction. These data suggest that Sld2 association with DNA is required for CMG assembly in S phase...
- Gary R, Park M, Nolan J, Cornelius H, Kozyreva O, Tran H, et al. A novel role in DNA metabolism for the binding of Fen1/Rad27 to PCNA and implications for genetic risk. Mol Cell Biol. 1999;19:5373-82 pubmed..These results suggest that phenotypically mild polymorphisms in DNA metabolic proteins can have dramatic consequences when combined. ..
- Kamimura Y, Masumoto H, Sugino A, Araki H. Sld2, which interacts with Dpb11 in Saccharomyces cerevisiae, is required for chromosomal DNA replication. Mol Cell Biol. 1998;18:6102-9 pubmed..These results strongly suggest the involvement of the Dpb11-Sld2 complex in a step close to the initiation of DNA replication. ..
- Langston L, Zhang D, Yurieva O, Georgescu R, Finkelstein J, Yao N, et al. CMG helicase and DNA polymerase Îµ form a functional 15-subunit holoenzyme for eukaryotic leading-strand DNA replication. Proc Natl Acad Sci U S A. 2014;111:15390-5 pubmed publisher..On its own, the Pol2 catalytic subunit of Pol Îµ is inefficient in CMG-dependent replication, but addition of the Dpb2 protein subunit ..
- Frei C, Gasser S. The yeast Sgs1p helicase acts upstream of Rad53p in the DNA replication checkpoint and colocalizes with Rad53p in S-phase-specific foci. Genes Dev. 2000;14:81-96 pubmed..The association of Rad53p with a chromatin subfraction is Sgs1p dependent, suggesting an important role for the helicase in the signal-transducing pathway that monitors replication fork progression. ..
- Williams J, Gehle D, Kunkel T. The role of RNase H2 in processing ribonucleotides incorporated during DNA replication. DNA Repair (Amst). 2017;53:52-58 pubmed publisher..mutant was expressed in wild type yeast or in a strain that also encodes a mutant allele of DNA polymerase Îµ (pol2-M644G) that enhances ribonucleotide incorporation during DNA replication...
- Johnson R, Klassen R, Prakash L, Prakash S. A Major Role of DNA Polymerase Î´ in Replication of Both the Leading and Lagging DNA Strands. Mol Cell. 2015;59:163-175 pubmed publisherGenetic studies with S.Â cerevisiae PolÎ´ (pol3-L612M) and PolÎµ (pol2-M644G) mutant alleles, each of which display a higher rate for the generation of a specific mismatch, have led to the conclusion that PolÎµ is the primary ..
- Williams L, Marjavaara L, Knowels G, Schultz E, Fox E, Chabes A, et al. dNTP pool levels modulate mutator phenotypes of error-prone DNA polymerase ? variants. Proc Natl Acad Sci U S A. 2015;112:E2457-66 pubmed publisher..Deletion of DUN1 (dun1?) suppresses the mutator phenotype of pol2-4 (encoding Pol ? proofreading deficiency) and is synthetically lethal with pol2-M644G (encoding altered Pol ? base ..
- Brooke R, Dumas L. Reconstitution of the Saccharomyces cerevisiae DNA primase-DNA polymerase protein complex in vitro. The 86-kDa subunit facilitates but is not required for complex formation. J Biol Chem. 1991;266:10093-8 pubmed
- Huang S, Williams J, Arana M, Kunkel T, Pommier Y. Topoisomerase I-mediated cleavage at unrepaired ribonucleotides generates DNA double-strand breaks. EMBO J. 2017;36:361-373 pubmed publisher..Taken together, these results define Top1 as a source of DSBs and genome instability when ribonucleotides incorporated by the replicative polymerases are not removed by RNase H2. ..
- Qiu C, Erinne O, Dave J, Cui P, Jin H, Muthukrishnan N, et al. High-Resolution Phenotypic Landscape of the RNA Polymerase II Trigger Loop. PLoS Genet. 2016;12:e1006321 pubmed publisher..Our structural genetics approach incorporates structural and phenotypic data for high-resolution dissection of transcription mechanisms and their evolution, and is readily applicable to other essential yeast proteins. ..
- Tumbale P, Williams J, Schellenberg M, Kunkel T, Williams R. Aprataxin resolves adenylated RNA-DNA junctions to maintain genome integrity. Nature. 2014;506:111-5 pubmed publisher..Together, these results indicate that accumulation of adenylated RNA-DNA may contribute to neurological disease. ..
- Navas T, Sanchez Y, Elledge S. RAD9 and DNA polymerase epsilon form parallel sensory branches for transducing the DNA damage checkpoint signal in Saccharomyces cerevisiae. Genes Dev. 1996;10:2632-43 pubmed..While RAD9, RAD24, and MEC3 are required to activate the DNA damage checkpoint when cells are in G1 or G2, POL2 is required to sense UV damage and replication blocks when cells are in S phase...
- Deshpande A, Ivanova I, Raykov V, Xue Y, Maringele L. Polymerase epsilon is required to maintain replicative senescence. Mol Cell Biol. 2011;31:1637-45 pubmed publisher..Every time resection and resynthesis switches, a fresh signal initiates, thus preventing checkpoint adaptation and ensuring the permanent character of senescence. ..
- Tseng S, Gabriel A, Teng S. Proofreading activity of DNA polymerase Pol2 mediates 3'-end processing during nonhomologous end joining in yeast. PLoS Genet. 2008;4:e1000060 pubmed publisher..Here, we use this system to examine DNA polymerases required for NHEJ in yeast. We demonstrate that Pol2 is another major DNA polymerase involved in imprecise end joining...
- Jain R, Vanamee E, Dzikovski B, Buku A, Johnson R, Prakash L, et al. An iron-sulfur cluster in the polymerase domain of yeast DNA polymerase ?. J Mol Biol. 2014;426:301-8 pubmed publisher..Pol? from Saccharomyces cerevisiae is composed of four subunits--Pol2, Dpb2, Dpb3, and Dpb4...
- Conover H, Lujan S, Chapman M, Cornelio D, Sharif R, Williams J, et al. Stimulation of Chromosomal Rearrangements by Ribonucleotides. Genetics. 2015;201:951-61 pubmed publisher..RNase H2 activity increases loss of heterozygosity (LOH) in Saccharomyces cerevisiae diploid strains harboring the pol2-M644G allele encoding a mutant version of DNA polymerase Îµ that increases ribonucleotide incorporation...
- 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. ..
- Ganai R, Osterman P, Johansson E. Yeast DNA polymerase Ïµ catalytic core and holoenzyme have comparable catalytic rates. J Biol Chem. 2015;290:3825-35 pubmed publisherThe holoenzyme of yeast DNA polymerase Ïµ (Pol Ïµ) consists of four subunits: Pol2, Dpb2, Dpb3, and Dpb4...
- Potenski C, Niu H, Sung P, Klein H. Avoidance of ribonucleotide-induced mutations by RNase H2 and Srs2-Exo1 mechanisms. Nature. 2014;511:251-4 pubmed publisher..Our results have implications for understanding the basis of Aicardi-Goutières syndrome, which stems from inactivation of the human RNase H2 complex. ..
- 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..Here we show that this rate is increased by 2-4-fold in pol2-4 rnh201Î” strains that are also defective in Pol É› proofreading...
- Kawasaki Y, Hiraga S, Sugino A. Interactions between Mcm10p and other replication factors are required for proper initiation and elongation of chromosomal DNA replication in Saccharomyces cerevisiae. Genes Cells. 2000;5:975-89 pubmed
- Chon H, Sparks J, Rychlik M, Nowotny M, Burgers P, Crouch R, et al. RNase H2 roles in genome integrity revealed by unlinking its activities. Nucleic Acids Res. 2013;41:3130-43 pubmed publisher..However, this AGS-related mutation accumulates 2-5 bp deletions at a very similar rate as the deletion strain. ..
- Santocanale C, Neecke H, Longhese M, Lucchini G, Plevani P. Mutations in the gene encoding the 34 kDa subunit of yeast replication protein A cause defective S phase progression. J Mol Biol. 1995;254:595-607 pubmed..Finally, rfa2 mutant cells have a mutator and hyper-recombination phenotype and are more sensitive to hydroxyurea and methyl-methane-sulfonate than wild-type cells. ..
- Flood C, Rodriguez G, Bao G, Shockley A, Kow Y, Crouse G. Replicative DNA polymerase Î´ but not Îµ proofreads errors in Cis and in Trans. PLoS Genet. 2015;11:e1005049 pubmed publisher..Proofreading mutations have been shown to result in tumor formation in both mice and humans; the results presented here can help explain the properties exhibited by those proofreading mutants. ..
- Haye J, Gammie A. The Eukaryotic Mismatch Recognition Complexes Track with the Replisome during DNA Synthesis. PLoS Genet. 2015;11:e1005719 pubmed publisher..Using yeast, we examined the dynamics during replication of the leading strand polymerase PolÎµ using Pol2 and the eukaryotic mismatch recognition complex using Msh2, the invariant protein involved in mismatch recognition...
- Azvolinsky A, Dunaway S, Torres J, Bessler J, Zakian V. The S. cerevisiae Rrm3p DNA helicase moves with the replication fork and affects replication of all yeast chromosomes. Genes Dev. 2006;20:3104-16 pubmed..Thus, rather than being recruited to its sites of action when replication forks stall at these sites, Rrm3p is likely a component of the replication fork apparatus. ..
- Hombauer H, Campbell C, Smith C, Desai A, Kolodner R. Visualization of eukaryotic DNA mismatch repair reveals distinct recognition and repair intermediates. Cell. 2011;147:1040-53 pubmed publisher..These findings suggest the presence of replication machinery-coupled and -independent pathways for mispair recognition by Msh2-Msh6, which direct formation of superstoichiometric Mlh1-Pms1 foci that represent sites of active MMR. ..
- Cho J, Huang S, Burgers P, Shuman S, Pommier Y, Jinks Robertson S. Parallel analysis of ribonucleotide-dependent deletions produced by yeast Top1 in vitro and in vivo. Nucleic Acids Res. 2016;44:7714-21 pubmed publisher..Our data fortify sequential Top1 cleavage as the mechanism for ribonucleotide-dependent deletions and provide new insight into the component steps of this process. ..
- Liberti S, LARREA A, Kunkel T. Exonuclease 1 preferentially repairs mismatches generated by DNA polymerase Î±. DNA Repair (Amst). 2013;12:92-6 pubmed publisher..of the lagging strand replicase, DNA polymerase Î´ (Pol Î´), than when combined with a mutator variant (pol2-M644G) of the leading strand replicase, DNA polymerase É› (Pol É›)...