Genomes and Genes
Gene Symbol: POL1
Description: DNA-directed DNA polymerase alpha catalytic subunit POL1
Alias: CDC17, CRT5, HPR3, DNA-directed DNA polymerase alpha catalytic subunit POL1
Species: Saccharomyces cerevisiae S288c
- Kuhn C, Geiger S, Baumli S, Gartmann M, Gerber J, Jennebach S, et al. Functional architecture of RNA polymerase I. Cell. 2007;131:1260-72 pubmed..In contrast to Pol II, Pol I has a strong intrinsic 3'-RNA cleavage activity, which requires the C-terminal domain of subunit A12.2 and, apparently, enables ribosomal RNA proofreading and 3'-end trimming. ..
- Miles J, Formosa T. Evidence that POB1, a Saccharomyces cerevisiae protein that binds to DNA polymerase alpha, acts in DNA metabolism in vivo. Mol Cell Biol. 1992;12:5724-35 pubmed..These phenotypes are consistent with defective DNA metabolism in cells lacking POB1 and strongly suggest that this DNA polymerase alpha-binding protein plays a role in accurately duplicating the genome in vivo. ..
- Qi H, Zakian V. The Saccharomyces telomere-binding protein Cdc13p interacts with both the catalytic subunit of DNA polymerase alpha and the telomerase-associated est1 protein. Genes Dev. 2000;14:1777-88 pubmed..Point mutations in either CDC13 or POL1 that reduced the Cdc13p-Pol1p interaction resulted in telomerase mediated telomere lengthening...
- Tanaka H, Katou Y, Yagura M, Saitoh K, Itoh T, Araki H, et al. Ctf4 coordinates the progression of helicase and DNA polymerase alpha. Genes Cells. 2009;14:807-20 pubmed publisher..These results lead us to propose that Ctf4 is a key connector between DNA helicase and Pol alpha and is required for the coordinated progression of the replisome. ..
- Klinge S, NÃºÃ±ez RamÃrez R, Llorca O, Pellegrini L. 3D architecture of DNA Pol alpha reveals the functional core of multi-subunit replicative polymerases. EMBO J. 2009;28:1978-87 pubmed publisher..Our combined findings provide a structural template for the common functional architecture of the three major replicative DNA polymerases. ..
- Zhou Y, Wang T. A coordinated temporal interplay of nucleosome reorganization factor, sister chromatin cohesion factor, and DNA polymerase alpha facilitates DNA replication. Mol Cell Biol. 2004;24:9568-79 pubmed..A mutation in a glycine residue in this N-terminal region of POL1 compromises the ability of Pol1p to associate with Spt16p and alters the temporal ordered association of Ctf4p with ..
- Johansson E, Garg P, Burgers P. The Pol32 subunit of DNA polymerase delta contains separable domains for processive replication and proliferating cell nuclear antigen (PCNA) binding. J Biol Chem. 2004;279:1907-15 pubmed..Pol32 binding, in vivo and in vitro, to the large subunit of DNA polymerase alpha, POL1, requires the carboxyl-proximal region of Pol32...
- Xu L, Petreaca R, Gasparyan H, Vu S, Nugent C. TEN1 is essential for CDC13-mediated telomere capping. Genetics. 2009;183:793-810 pubmed publisher..These results emphasize that Cdc13 relies on Ten1 to execute its essential function, but leave open the possibility that Ten1 has a Cdc13-independent role in DNA replication. ..
- Chandra A, Hughes T, Nugent C, Lundblad V. Cdc13 both positively and negatively regulates telomere replication. Genes Dev. 2001;15:404-14 pubmed..Thus, Cdc13 coordinates synthesis of both strands of the telomere by first recruiting telomerase and subsequently limiting G-strand synthesis by telomerase in response to C-strand replication. ..
- Hanna J, Kroll E, Lundblad V, Spencer F. Saccharomyces cerevisiae CTF18 and CTF4 are required for sister chromatid cohesion. Mol Cell Biol. 2001;21:3144-58 pubmed..The requirement for CTF4 and CTF18 in robust cohesion identifies novel roles for replication accessory proteins in this process. ..
- Gutierrez P, Wang T. Genomic instability induced by mutations in Saccharomyces cerevisiae POL1. Genetics. 2003;165:65-81 pubmed..Here we examined the effect of two mutations in S. cerevisiae POL1, pol1-1 and pol1-17, on a microsatellite (GT)(16) tract...
- Becker J, Nguyen H, Wang X, Bielinsky A. Mcm10 deficiency causes defective-replisome-induced mutagenesis and a dependency on error-free postreplicative repair. Cell Cycle. 2014;13:1737-48 pubmed publisher..Furthermore, we demonstrate that deficiencies in priming, induced by a pol1-1 mutation, also resulted in DRIM, but not in error-free PRR...
- Grossi S, Puglisi A, Dmitriev P, Lopes M, Shore D. Pol12, the B subunit of DNA polymerase alpha, functions in both telomere capping and length regulation. Genes Dev. 2004;18:992-1006 pubmed..relaxed telomere length regulation, and the identification of Pol12, the B subunit of the DNA polymerase alpha (Pol1)-primase complex, as a new factor involved in this process...
- Simon A, Zhou J, Perera R, van Deursen F, Evrin C, Ivanova M, et al. A Ctf4 trimer couples the CMG helicase to DNA polymerase Î± in the eukaryotic replisome. Nature. 2014;510:293-297 pubmed publisher..The ability of Ctf4 to act as a platform for multivalent interactions illustrates a mechanism for the concurrent recruitment of factors that act together at the fork. ..
- Hiraga S, Hagihara Hayashi A, Ohya T, Sugino A. DNA polymerases alpha, delta, and epsilon localize and function together at replication forks in Saccharomyces cerevisiae. Genes Cells. 2005;10:297-309 pubmed..These data collectively suggest that bidirectional replication occurs at specific foci in yeast chromosomes and that pol alpha, -delta, and -epsilon localize and function together at multiple replication forks during S phase. ..
- Yano R, Oakes M, Yamaghishi M, Dodd J, Nomura M. Cloning and characterization of SRP1, a suppressor of temperature-sensitive RNA polymerase I mutations, in Saccharomyces cerevisiae. Mol Cell Biol. 1992;12:5640-51 pubmed..We suggest that SRP1 is a component of a larger macromolecular complex associated with the nuclear envelope and interacts with Pol I either directly or indirectly through other components in the structure containing SRP1. ..
- Gibson D, Bell S, Aparicio O. Cell cycle execution point analysis of ORC function and characterization of the checkpoint response to ORC inactivation in Saccharomyces cerevisiae. Genes Cells. 2006;11:557-73 pubmed..We discuss the potential significance of these overlapping checkpoints and the impact of our findings on previously postulated role(s) of ORCs in other cell cycle functions. ..
- Buck S, Maqani N, Matecic M, Hontz R, Fine R, Li M, et al. RNA Polymerase I and Fob1 contributions to transcriptional silencing at the yeast rDNA locus. Nucleic Acids Res. 2016;44:6173-84 pubmed publisher..We conclude that Fob1 and Pol I make independent contributions to establishment of silencing, though Pol I also reinforces Fob1-dependent silencing. ..
- Schlesinger M, Formosa T. POB3 is required for both transcription and replication in the yeast Saccharomyces cerevisiae. Genetics. 2000;155:1593-606 pubmed..interactions were observed between pob3 mutations and the genes encoding several DNA replication factors, including POL1, CTF4, DNA2, and CHL12...
- Peyroche G, Milkereit P, Bischler N, Tschochner H, Schultz P, Sentenac A, et al. The recruitment of RNA polymerase I on rDNA is mediated by the interaction of the A43 subunit with Rrn3. EMBO J. 2000;19:5473-82 pubmed..The existence of mammalian orthologues of A43 and Rrn3 suggests evolutionary conservation of the molecular mechanisms underlying rDNA transcription in eukaryotes. ..
- Philippi A, Steinbauer R, Reiter A, Fath S, Leger Silvestre I, Milkereit P, et al. TOR-dependent reduction in the expression level of Rrn3p lowers the activity of the yeast RNA Pol I machinery, but does not account for the strong inhibition of rRNA production. Nucleic Acids Res. 2010;38:5315-26 pubmed publisher..However, our analysis reveals that the dramatic reduction of rRNA synthesis in the immediate cellular response to impaired TOR signalling cannot be explained by the simple down-regulation of Rrn3p and Pol I-Rrn3p levels. ..
- Bhat W, Boutin G, Rufiange A, Nourani A. Casein kinase 2 associates with the yeast chromatin reassembly factor Spt2/Sin1 to regulate its function in the repression of spurious transcription. Mol Cell Biol. 2013;33:4198-211 pubmed publisher..Taken together, our data suggest that CK2 regulates the function of Spt2 by modulating its interaction with chromatin and the histone chaperone Spt6. ..
- Ramey C, Howar S, Adkins M, Linger J, Spicer J, Tyler J. Activation of the DNA damage checkpoint in yeast lacking the histone chaperone anti-silencing function 1. Mol Cell Biol. 2004;24:10313-27 pubmed
- Hovland P, Tecklenberg M, Sclafani R. Overexpression of the protein kinase Pak1 suppresses yeast DNA polymerase mutations. Mol Gen Genet. 1997;256:45-53 pubmed..The phenotype of the suppressed cdc17-1 cells indicates that Pak1 suppression is inefficient and does not restore the wild-type phenotype...
- Chen L, Madura K. Degradation of specific nuclear proteins occurs in the cytoplasm in Saccharomyces cerevisiae. Genetics. 2014;197:193-7 pubmed publisher..We report here that two well-characterized nuclear proteins are stabilized in nuclear export mutants in Saccharomyces cerevisiae. The requirement for nuclear export defines a new regulatory step in intracellular proteolysis...
- Kubota T, Hiraga S, Yamada K, Lamond A, Donaldson A. Quantitative proteomic analysis of chromatin reveals that Ctf18 acts in the DNA replication checkpoint. Mol Cell Proteomics. 2011;10:M110.005561 pubmed publisher..Identification of Ctf18 as a checkpoint protein highlights the usefulness of chromatin proteomic analysis for understanding the in vivo function of proteins that mediate chromatin transactions. ..
- Brooke R, Singhal R, Hinkle D, Dumas L. Purification and characterization of the 180- and 86-kilodalton subunits of the Saccharomyces cerevisiae DNA primase-DNA polymerase protein complex. The 180-kilodalton subunit has both DNA polymerase and 3'----5'-exonuclease activities. J Biol Chem. 1991;266:3005-15 pubmed..cerevisiae as compared with the properties of preparations from Drosophila cells. In particular, the 3'----5'-exonuclease activity associated with the yeast catalytic DNA polymerase subunit was not masked by the 86-kDa subunit. ..
- Tseng S, Lin J, Teng S. The telomerase-recruitment domain of the telomere binding protein Cdc13 is regulated by Mec1p/Tel1p-dependent phosphorylation. Nucleic Acids Res. 2006;34:6327-36 pubmed..These results demonstrate the telomerase recruitment domain of Cdc13p as an important new telomere-specific target of Mec1p/Tel1p. ..
- Huang M, Le Douarin B, Henry C, Galibert F. The Saccharomyces cerevisiae protein YJR043C (Pol32) interacts with the catalytic subunit of DNA polymerase alpha and is required for cell cycle progression in G2/M. Mol Gen Genet. 1999;260:541-50 pubmed..In two-hybrid assays, the YJR043c gene product specifically interacted with Pol1, the catalytic subunit of DNA polymerase alpha...
- Wittmeyer J, Formosa T. The Saccharomyces cerevisiae DNA polymerase alpha catalytic subunit interacts with Cdc68/Spt16 and with Pob3, a protein similar to an HMG1-like protein. Mol Cell Biol. 1997;17:4178-90 pubmed..Two proteins that bound to the catalytic subunit of DNA polymerase alpha (Pol1 protein) are encoded by the essential genes CDC68/SPT16 and POB3...
- 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..The LOH rate was not elevated in strains carrying the pol1-L868M or pol3-L612M alleles that result in increased incorporation of ribonucleotides during DNA synthesis by ..
- Weinreich M, Stillman B. Cdc7p-Dbf4p kinase binds to chromatin during S phase and is regulated by both the APC and the RAD53 checkpoint pathway. EMBO J. 1999;18:5334-46 pubmed..Cdc7p-Dbf4p efficiently phosphorylates several proteins that are required for the initiation of DNA replication, including five of the six Mcm proteins and the p180 subunit of DNA polymerase alpha-primase. ..
- Rudner A, Murray A. Phosphorylation by Cdc28 activates the Cdc20-dependent activity of the anaphase-promoting complex. J Cell Biol. 2000;149:1377-90 pubmed..We show that, like cdc28 mutants, cdc5 mutants affect APC phosphorylation in vivo. However, although Cdc5 can phosphorylate Cdc16 and Cdc27 in vitro, this in vitro phosphorylation does not occur on in vivo sites of phosphorylation. ..
- Lottersberger F, Rubert F, Baldo V, Lucchini G, Longhese M. Functions of Saccharomyces cerevisiae 14-3-3 proteins in response to DNA damage and to DNA replication stress. Genetics. 2003;165:1717-32 pubmed..Finally, the bmh1-169 bmh2Delta and bmh1-170 bmh2Delta mutants show increased rates of spontaneous gross chromosomal rearrangements, indicating that Bmh proteins are required to suppress genome instability. ..
- Plevani P, Foiani M, Valsasnini P, Badaracco G, Cheriathundam E, Chang L. Polypeptide structure of DNA primase from a yeast DNA polymerase-primase complex. J Biol Chem. 1985;260:7102-7 pubmed..Two polypeptides of 58 and 48 kDa co-fractionated with the free yeast DNA primase. From sucrose gradient analysis we estimate a molecular weight of 110 kDa for the native DNA primase. ..
- Longhese M, Fraschini R, Plevani P, Lucchini G. Yeast pip3/mec3 mutants fail to delay entry into S phase and to slow DNA replication in response to DNA damage, and they define a functional link between Mec3 and DNA primase. Mol Cell Biol. 1996;16:3235-44 pubmed
- Fumasoni M, Zwicky K, Vanoli F, Lopes M, Branzei D. Error-free DNA damage tolerance and sister chromatid proximity during DNA replication rely on the PolÎ±/Primase/Ctf4 Complex. Mol Cell. 2015;57:812-23 pubmed publisher..Defects in this event impact on replication fork architecture and sister chromatid proximity, and represent a frequent source of chromosome lesions upon replication dysfunctions. ..
- Albert B, LÃ©ger Silvestre I, Normand C, Ostermaier M, PÃ©rez FernÃ¡ndez J, Panov K, et al. RNA polymerase I-specific subunits promote polymerase clustering to enhance the rRNA gene transcription cycle. J Cell Biol. 2011;192:277-93 pubmed publisher..Together our data suggest that localized rRNA production results in spatially constrained rRNA production, which is instrumental for nucleolar assembly. ..
- Budd M, Wittrup K, Bailey J, Campbell J. DNA polymerase I is required for premeiotic DNA replication and sporulation but not for X-ray repair in Saccharomyces cerevisiae. Mol Cell Biol. 1989;9:365-76 pubmed..These results do not, however, rule out essential roles for DNA polymerase II or III or both in addition to that for DNA polymerase I. ..
- Holmes A, Haber J. Double-strand break repair in yeast requires both leading and lagging strand DNA polymerases. Cell. 1999;96:415-24 pubmed..Surprisingly, mutants of lagging strand replication, DNA polymerase alpha (pol1-17), DNA primase (pri2-1), and Rad27p (rad27 delta) also greatly inhibit completion of DSB repair, even in G1-..
- Samora C, Saksouk J, Goswami P, Wade B, Singleton M, Bates P, et al. Ctf4 Links DNA Replication with Sister Chromatid Cohesion Establishment by Recruiting the Chl1 Helicase to the Replisome. Mol Cell. 2016;63:371-84 pubmed publisher..Our results reveal how Ctf4 forms a replisomal interaction hub that coordinates replication fork progression and sister chromatid cohesion establishment. ..
- Villa F, Simon A, Ortiz Bazan M, Kilkenny M, Wirthensohn D, Wightman M, et al. Ctf4 Is a Hub in the Eukaryotic Replisome that Links Multiple CIP-Box Proteins to the CMG Helicase. Mol Cell. 2016;63:385-96 pubmed publisher..Most strikingly, Ctf4-dependent recruitment of CIP-box proteins couples other processes to DNA synthesis, including rDNA copy-number regulation. ..
- Bouchoux C, Hautbergue G, Grenetier S, Carles C, Riva M, Goguel V. CTD kinase I is involved in RNA polymerase I transcription. Nucleic Acids Res. 2004;32:5851-60 pubmed..The results suggest that CTDK-I might participate in the regulation of distinct nuclear transcriptional machineries, thus playing a role in the adaptation of the global transcriptional response to growth signalling. ..
- Sun J, Yang Y, Wan K, Mao N, Yu T, Lin Y, et al. Structural bases of dimerization of yeast telomere protein Cdc13 and its interaction with the catalytic subunit of DNA polymerase ?. Cell Res. 2011;21:258-74 pubmed publisher..basis of the interaction between the Cdc13 N-terminal OB fold and the catalytic subunit of DNA polymerase ? (Pol1), and demonstrated a role for Cdc13 dimerization in Pol1 binding...
- Anbalagan S, Bonetti D, Lucchini G, Longhese M. Rif1 supports the function of the CST complex in yeast telomere capping. PLoS Genet. 2011;7:e1002024 pubmed publisher..Thus, these data highlight a novel role for Rif1 in assisting the essential telomere protection function of the CST complex. ..
- Huang M, Zhou Z, Elledge S. The DNA replication and damage checkpoint pathways induce transcription by inhibition of the Crt1 repressor. Cell. 1998;94:595-605 pubmed..The inhibition of an autoregulatory repressor in response to DNA damage is a strategy conserved throughout prokaryotic and eukaryotic evolution. ..
- Johnson L, Snyder M, Chang L, Davis R, Campbell J. Isolation of the gene encoding yeast DNA polymerase I. Cell. 1985;43:369-77 pubmed..Examination of the germinated spores containing the disrupted gene reveals a defect in nuclear division and a terminal phenotype typical of replication mutants. ..
- Lydall D, Weinert T. G2/M checkpoint genes of Saccharomyces cerevisiae: further evidence for roles in DNA replication and/or repair. Mol Gen Genet. 1997;256:638-51 pubmed..rate of yeast strains that are defective in the DNA replication/repair proteins Rfc1p (cdc44), DNA pol alpha (cdc17) and DNA pol delta (cdc2) but has much weaker effects on cdc6, cdc9, cdc15 and CDC4 strains...
- Formosa T, Nittis T. Suppressors of the temperature sensitivity of DNA polymerase alpha mutations in Saccharomyces cerevisiae. Mol Gen Genet. 1998;257:461-8 pubmedWe have isolated two high copy, allele-specific suppressors of the temperature sensitivity of mutations in POL1, the gene that encodes the catalytic subunit of DNA polymerase alpha in the yeast Saccharomyces cerevisiae...
- Tanaka T, Nasmyth K. Association of RPA with chromosomal replication origins requires an Mcm protein, and is regulated by Rad53, and cyclin- and Dbf4-dependent kinases. EMBO J. 1998;17:5182-91 pubmed..Thus, in the presence of active S-CDKs and Dbf4/Cdc7, Mcms may open origins and thereby facilitate the loading of RPA. ..
- van Deursen F, Sengupta S, De Piccoli G, Sanchez Diaz A, Labib K. Mcm10 associates with the loaded DNA helicase at replication origins and defines a novel step in its activation. EMBO J. 2012;31:2195-206 pubmed publisher..These findings indicate that Mcm10 is required for a novel step during activation of the Cdc45-MCM-GINS helicase at DNA replication origins. ..
- Laribee R, Hosni Ahmed A, Workman J, Chen H. Ccr4-not regulates RNA polymerase I transcription and couples nutrient signaling to the control of ribosomal RNA biogenesis. PLoS Genet. 2015;11:e1005113 pubmed publisher..Collectively, these data demonstrate a novel role for Ccr4-Not in Pol I transcriptional regulation that is required for bridging mTORC1 signaling to ribosomal RNA synthesis. ..
- Storici F, Bebenek K, Kunkel T, Gordenin D, Resnick M. RNA-templated DNA repair. Nature. 2007;447:338-41 pubmed
- Pavlov Y, Frahm C, Nick McElhinny S, Niimi A, Suzuki M, Kunkel T. Evidence that errors made by DNA polymerase alpha are corrected by DNA polymerase delta. Curr Biol. 2006;16:202-7 pubmed..L868M pol alpha copies DNA in vitro with normal activity and processivity but with reduced fidelity. In vivo, the pol1-L868M allele confers a mutator phenotype...
- Borges V, Smith D, Whitehouse I, Uhlmann F. An Eco1-independent sister chromatid cohesion establishment pathway in S. cerevisiae. Chromosoma. 2013;122:121-34 pubmed publisher..Thus, Ctf4 and Chl1 delineate an additional acetylation-independent pathway that might hold important clues as to the mechanism of sister chromatid cohesion establishment...
- Garber P, Rine J. Overlapping roles of the spindle assembly and DNA damage checkpoints in the cell-cycle response to altered chromosomes in Saccharomyces cerevisiae. Genetics. 2002;161:521-34 pubmed..Thus the specificity of this checkpoint may be more limited than previously recognized. ..
- Davis L, Barbera M, McDonnell A, McIntyre K, Sternglanz R, Jin Q, et al. The Saccharomyces cerevisiae MUM2 gene interacts with the DNA replication machinery and is required for meiotic levels of double strand breaks. Genetics. 2001;157:1179-89 pubmed..Given the near-wild-type levels of meiotic gene expression, pairing, and synapsis, we suggest that the reduction in DNA replication is directly responsible for the reduced level of DSBs and meiotic recombination. ..
- 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
- Ricke R, Bielinsky A. A conserved Hsp10-like domain in Mcm10 is required to stabilize the catalytic subunit of DNA polymerase-alpha in budding yeast. J Biol Chem. 2006;281:18414-25 pubmed..mcm10-1 mutants, depletion of Mcm10 results in degradation of the catalytic subunit of pol-alpha, Cdc17/Pol1, regardless of whether cells are in G(1), S, or G(2) phase...