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Gene Review

POL1  -  DNA-directed DNA polymerase alpha...

Saccharomyces cerevisiae S288c

Synonyms: CDC17, CRT5, DNA polymerase I subunit A, DNA polymerase alpha catalytic subunit A, DNA polymerase alpha:primase complex p180 subunit, ...
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High impact information on POL1


Biological context of POL1

  • Analysis of mRNA levels in cell-cycle-synchronized cultures reveals that the RNR1 mRNA is tightly cell-cycle regulated, fluctuating 15- to 30-fold, and is coordinately regulated with the POL1 mRNA, being expressed in the late G1 and S phases of the cell cycle [3].
  • Instead, and again unlike mutations affecting POL1, pol12-216 is lethal in combination with a mutation in the telomere end-binding and capping protein Stn1 [4].
  • Mutations in POL1 and POL3 also activate RNR expression, indicating that the DNA damage sensory network may respond directly to blocks in DNA synthesis [5].
  • We 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 [6].
  • The cloned DNA polymerase I gene has been used to map the POL1 locus on the left arm of chromosome XIV, between MET4 and TOP2 [7].

Associations of POL1 with chemical compounds

  • MCBs are both necessary and sufficient for the late G1-specific transcription of the TMP1 thymidylate synthase and POL1 DNA polymerase genes [8].
  • CDC8 was also found to be inducible by DNA damage, but POL1 and URA3 were not inducible by 4-nitroquinoline 1-oxide [9].
  • A pol1 temperature-sensitive mutation, encoding a DNA-polymerase-primase complex with altered stability, has a single base-pair substitution that changes the glycine at position 493 to a positively charged arginine [10].
  • In each mutant, a single bp substitution, causing the replacement of Gly residues by either Asp (cdc17-1, cdc17-2) or Glu (hpr3) in yeast DNA polymerase I is responsible for the ts phenotype [11].

Physical interactions of POL1

  • CDC68 also interacted genetically with POL1 and CTF4 mutations; the maximum permissive temperature of double mutants was lower than for any single mutant [12].
  • Pol1p was shown to interact with Cdc13p [13].

Regulatory relationships of POL1

  • We propose that Cdc13p's interaction with Est1p promotes TG(1-3) strand lengthening by telomerase and its interaction with Pol1p promotes C(1-3)A strand resynthesis by DNA polymerase alpha [14].

Other interactions of POL1

  • Overexpression of Cdc68 in a pol1 mutant strain dramatically decreased cell viability, consistent with the formation or modulation of an essential complex by these proteins in vivo [12].
  • Repair synthesis in nuclear extracts of pol1, pol2, and pol3 temperature-sensitive mutants was normal at permissive temperatures [15].
  • POL1 (DNA polymerase I) and CDC8 (thymidylate kinase) transcription were unaltered, while histone H2B transcripts actually decreased by half [16].
  • Unlike many POL1 and POL12 mutations, which also cause telomere elongation, the pol12-216 mutation described here does not lead to either reduced Pol1 function, increased telomeric single-stranded DNA, or a reduction in telomeric gene silencing [4].
  • The POL1 gene is located on chromosome XIV approximately 2 centimorgans away from met4 [17].

Analytical, diagnostic and therapeutic context of POL1


  1. DNA polymerase III, a second essential DNA polymerase, is encoded by the S. cerevisiae CDC2 gene. Sitney, K.C., Budd, M.E., Campbell, J.L. Cell (1989) [Pubmed]
  2. CDC17: an essential gene that prevents telomere elongation in yeast. Carson, M.J., Hartwell, L. Cell (1985) [Pubmed]
  3. Two genes differentially regulated in the cell cycle and by DNA-damaging agents encode alternative regulatory subunits of ribonucleotide reductase. Elledge, S.J., Davis, R.W. Genes Dev. (1990) [Pubmed]
  4. Pol12, the B subunit of DNA polymerase alpha, functions in both telomere capping and length regulation. Grossi, S., Puglisi, A., Dmitriev, P.V., Lopes, M., Shore, D. Genes Dev. (2004) [Pubmed]
  5. DNA damage and cell cycle regulation of ribonucleotide reductase. Elledge, S.J., Zhou, Z., Allen, J.B., Navas, T.A. Bioessays (1993) [Pubmed]
  6. Suppressors of the temperature sensitivity of DNA polymerase alpha mutations in Saccharomyces cerevisiae. Formosa, T., Nittis, T. Mol. Gen. Genet. (1998) [Pubmed]
  7. Genetic mapping of the Saccharomyces cerevisiae DNA polymerase I gene and characterization of a pol1 temperature-sensitive mutant altered in DNA primase-polymerase complex stability. Lucchini, G., Mazza, C., Scacheri, E., Plevani, P. Mol. Gen. Genet. (1988) [Pubmed]
  8. A central role for SWI6 in modulating cell cycle Start-specific transcription in yeast. Dirick, L., Moll, T., Auer, H., Nasmyth, K. Nature (1992) [Pubmed]
  9. Identification and isolation of the gene encoding the small subunit of ribonucleotide reductase from Saccharomyces cerevisiae: DNA damage-inducible gene required for mitotic viability. Elledge, S.J., Davis, R.W. Mol. Cell. Biol. (1987) [Pubmed]
  10. DNA polymerase I gene of Saccharomyces cerevisiae: nucleotide sequence, mapping of a temperature-sensitive mutation, and protein homology with other DNA polymerases. Pizzagalli, A., Valsasnini, P., Plevani, P., Lucchini, G. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  11. Nucleotide sequence and characterization of temperature-sensitive pol1 mutants of Saccharomyces cerevisiae. Lucchini, G., Falconi, M.M., Pizzagalli, A., Aguilera, A., Klein, H.L., Plevani, P. Gene (1990) [Pubmed]
  12. The Saccharomyces cerevisiae DNA polymerase alpha catalytic subunit interacts with Cdc68/Spt16 and with Pob3, a protein similar to an HMG1-like protein. Wittmeyer, J., Formosa, T. Mol. Cell. Biol. (1997) [Pubmed]
  13. Interaction of Saccharomyces Cdc13p with Pol1p, Imp4p, Sir4p and Zds2p is involved in telomere replication, telomere maintenance and cell growth control. Hsu, C.L., Chen, Y.S., Tsai, S.Y., Tu, P.J., Wang, M.J., Lin, J.J. Nucleic Acids Res. (2004) [Pubmed]
  14. The Saccharomyces telomere-binding protein Cdc13p interacts with both the catalytic subunit of DNA polymerase alpha and the telomerase-associated est1 protein. Qi, H., Zakian, V.A. Genes Dev. (2000) [Pubmed]
  15. DNA repair synthesis during base excision repair in vitro is catalyzed by DNA polymerase epsilon and is influenced by DNA polymerases alpha and delta in Saccharomyces cerevisiae. Wang, Z., Wu, X., Friedberg, E.C. Mol. Cell. Biol. (1993) [Pubmed]
  16. Deoxyribonucleotides are maintained at normal levels in a yeast thioredoxin mutant defective in DNA synthesis. Muller, E.G. J. Biol. Chem. (1994) [Pubmed]
  17. Temperature-sensitive mutations in the yeast DNA polymerase I gene. Budd, M., Campbell, J.L. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  18. 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. Huang, M.E., Le Douarin, B., Henry, C., Galibert, F. Mol. Gen. Genet. (1999) [Pubmed]
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