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Gene Review

POL3  -  DNA-directed DNA polymerase delta POL3

Saccharomyces cerevisiae S288c

Synonyms: CDC2, D2366, DNA polymerase III, DNA polymerase delta catalytic subunit, HPR6, ...
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Disease relevance of CDC2


High impact information on CDC2

  • In the absence of p97-Ufd1-Npl4 function, microtubules in Xenopus egg extracts remain as monopolar spindles attached to condensed chromosomes after Cdc2 kinase activity has returned to the interphase level [6].
  • The nim1-catalyzed phosphorylation of the wee1 protein occurs in its C-terminal region and leads to a substantial drop in its activity as a cdc2-specific tyrosine kinase [7].
  • SGV1 encodes a CDC28/cdc2-related kinase required for a G alpha subunit-mediated adaptive response to pheromone in S. cerevisiae [8].
  • Since the S. cerevisiae CDC2 gene has recently been shown to have DNA sequence similarity to the active site regions of other known DNA polymerases, but to nevertheless be different from DNA polymerase I, we examined cdc2 mutants for the presence of DNA polymerases II and III [9].
  • These findings suggest that ORC functions are conserved among eukaryotes and provide evidence that Cdc2 controls DNA replication initiation by acting directly at chromosomal origins [10].

Biological context of CDC2

  • These results suggest that in human cells, two different CDC2-like kinases may regulate the cell cycle at distinct stages [11].
  • In this paper we determine partial amino acid sequences of the 125 and 55 kDa polypeptides and find that they match parts of the amino acid sequences predicted from the nucleotide sequence of the CDC2 and HYS2 genes respectively [12].
  • The temperature-sensitive growth phenotype of hys2-1 and hys2-2 mutations could be suppressed by the CDC2 gene on a multicopy plasmid [12].
  • The nucleotide sequence of a 5 kb EcoRI-NcoI fragment of chromosome IV, contiguous to gene POL3 (CDC2), has been determined [13].
  • Thermal inactivation of DNA polymerase delta in pol3 nuclear extracts enhanced DNA repair synthesis approximately 2-fold, an effect which could be specifically reversed by the addition of purified yeast DNA polymerase delta to the extract [14].

Anatomical context of CDC2


Associations of CDC2 with chemical compounds


Physical interactions of CDC2


Regulatory relationships of CDC2


Other interactions of CDC2

  • Cloning of a human cDNA encoding a CDC2-related kinase by complementation of a budding yeast cdc28 mutation [11].
  • Such an involvement was previously suggested by in vivo analysis for CDC2 but was less clear for CDC16 [29].
  • The second subunit of DNA polymerase III (delta) is encoded by the HYS2 gene in Saccharomyces cerevisiae [12].
  • New alleles of the CDC2 and CDC17 genes were recovered among these mutants [30].
  • The mutator effects of mutations in the DNA polymerase delta (POL3) gene and the recombinational repair RAD52 gene were studied in combination with mismatch repair defects [31].

Analytical, diagnostic and therapeutic context of CDC2

  • DNA polymerase III (delta) of Saccharomyces cerevisiae is purified as a complex of at least two polypeptides with molecular masses of 125 and 55 kDa as judged by SDS-PAGE [12].
  • Through the use of gel-filtration chromatography, we have studied the interaction of the model template-primer system poly(dA).(dT)16 (40:1) with yeast DNA polymerase III and with PCNAs [32].
  • Southern blot analysis, as well as isolation of another cDNA clone, cdc2ZmB, which is 96% identical to cdc2ZmA, indicates that maize has multiple cdc2 genes [33].
  • Studies of expression of the maize cdc2 gene(s) by Northern blot analysis indicated a correlation between the abundance of cdc2 mRNA and the proliferative state of the tissue [33].
  • Five putative cleavage sites of this protease in Ty3 GAG3 and GAG3-POL3 polyproteins were defined by amino-terminal sequence analysis [34].


  1. Structure-function relationship of the eukaryotic DNA replication factor, proliferating cell nuclear antigen. Fukuda, K., Morioka, H., Imajou, S., Ikeda, S., Ohtsuka, E., Tsurimoto, T. J. Biol. Chem. (1995) [Pubmed]
  2. The Cys-His motif of Ty3 NC can be contributed by Gag3 or Gag3-Pol3 polyproteins. Orlinsky, K.J., Sandmeyer, S.B. J. Virol. (1994) [Pubmed]
  3. PITALRE, a nuclear CDC2-related protein kinase that phosphorylates the retinoblastoma protein in vitro. Graña, X., De Luca, A., Sang, N., Fu, Y., Claudio, P.P., Rosenblatt, J., Morgan, D.O., Giordano, A. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  4. Activation of RNA polymerase II by topologically linked DNA-tracking proteins. Ouhammouch, M., Sayre, M.H., Kadonaga, J.T., Geiduschek, E.P. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  5. Programmed +1 frameshifting stimulated by complementarity between a downstream mRNA sequence and an error-correcting region of rRNA. Li, Z., Stahl, G., Farabaugh, P.J. RNA (2001) [Pubmed]
  6. The AAA-ATPase Cdc48/p97 regulates spindle disassembly at the end of mitosis. Cao, K., Nakajima, R., Meyer, H.H., Zheng, Y. Cell (2003) [Pubmed]
  7. Negative regulation of the wee1 protein kinase by direct action of the nim1/cdr1 mitotic inducer. Coleman, T.R., Tang, Z., Dunphy, W.G. Cell (1993) [Pubmed]
  8. SGV1 encodes a CDC28/cdc2-related kinase required for a G alpha subunit-mediated adaptive response to pheromone in S. cerevisiae. Irie, K., Nomoto, S., Miyajima, I., Matsumoto, K. Cell (1991) [Pubmed]
  9. 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]
  10. Interaction of Cdc2 and Cdc18 with a fission yeast ORC2-like protein. Leatherwood, J., Lopez-Girona, A., Russell, P. Nature (1996) [Pubmed]
  11. Cloning of a human cDNA encoding a CDC2-related kinase by complementation of a budding yeast cdc28 mutation. Ninomiya-Tsuji, J., Nomoto, S., Yasuda, H., Reed, S.I., Matsumoto, K. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  12. The second subunit of DNA polymerase III (delta) is encoded by the HYS2 gene in Saccharomyces cerevisiae. Hashimoto, K., Nakashima, N., Ohara, T., Maki, S., Sugino, A. Nucleic Acids Res. (1998) [Pubmed]
  13. Sequence of the PHO2-POL3 (CDC2) region of chromosome IV of Saccharomyces cerevisiae. Simon, M., Bénit, P., Vassal, A., Dubois, C., Faye, G. Yeast (1994) [Pubmed]
  14. 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]
  15. Homology probing: identification of cDNA clones encoding members of the protein-serine kinase family. Hanks, S.K. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  16. Yeast as a model system for mammalian seven-transmembrane segment receptors. Jeansonne, N.E. Proc. Soc. Exp. Biol. Med. (1994) [Pubmed]
  17. Requirement for p34cdc2 kinase is restricted to mitosis in the mammalian cdc2 mutant FT210. Hamaguchi, J.R., Tobey, R.A., Pines, J., Crissman, H.A., Hunter, T., Bradbury, E.M. J. Cell Biol. (1992) [Pubmed]
  18. Complementation of a yeast cell cycle mutant by an alfalfa cDNA encoding a protein kinase homologous to p34cdc2. Hirt, H., Páy, A., Györgyey, J., Bakó, L., Németh, K., Bögre, L., Schweyen, R.J., Heberle-Bors, E., Dudits, D. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  19. A dependent pathway of gene functions leading to chromosome segregation in Saccharomyces cerevisiae. Wood, J.S., Hartwell, L.H. J. Cell Biol. (1982) [Pubmed]
  20. Involvement of the yeast DNA polymerase delta in DNA repair in vivo. Giot, L., Chanet, R., Simon, M., Facca, C., Faye, G. Genetics (1997) [Pubmed]
  21. S-phase feedback control in budding yeast independent of tyrosine phosphorylation of p34cdc28. Sorger, P.K., Murray, A.W. Nature (1992) [Pubmed]
  22. Spindle pole body separation in Saccharomyces cerevisiae requires dephosphorylation of the tyrosine 19 residue of Cdc28. Lim, H.H., Goh, P.Y., Surana, U. Mol. Cell. Biol. (1996) [Pubmed]
  23. Saccharomyces cerevisiae cdc2 mutants fail to replicate approximately one-third of their nuclear genome. Conrad, M.N., Newlon, C.S. Mol. Cell. Biol. (1983) [Pubmed]
  24. Candida albicans CDK1 and CYB1: cDNA homologues of the cdc2/CDC28 and cdc13/CLB1/CLB2 cell cycle control genes. Damagnez, V., Cottarel, G. Gene (1996) [Pubmed]
  25. Functionally homologous DNA replication genes in fission and budding yeast. Sánchez, M., Calzada, A., Bueno, A. J. Cell. Sci. (1999) [Pubmed]
  26. Transposon Tn5 excision in yeast: influence of DNA polymerases alpha, delta, and epsilon and repair genes. Gordenin, D.A., Malkova, A.L., Peterzen, A., Kulikov, V.N., Pavlov, Y.I., Perkins, E., Resnick, M.A. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  27. The yeast analog of mammalian cyclin/proliferating-cell nuclear antigen interacts with mammalian DNA polymerase delta. Bauer, G.A., Burgers, P.M. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  28. Reversible histone modifications and the chromosome cell cycle. Bradbury, E.M. Bioessays (1992) [Pubmed]
  29. Isolation of yeast DNA replication mutants in permeabilized cells. Kuo, C., Nuang, H., Campbell, J.L. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  30. Genetic control of intrachromosomal recombination in Saccharomyces cerevisiae. I. Isolation and genetic characterization of hyper-recombination mutations. Aguilera, A., Klein, H.L. Genetics (1988) [Pubmed]
  31. The prevention of repeat-associated deletions in Saccharomyces cerevisiae by mismatch repair depends on size and origin of deletions. Tran, H.T., Gordenin, D.A., Resnick, M.A. Genetics (1996) [Pubmed]
  32. Protein-protein interactions of yeast DNA polymerase III with mammalian and yeast proliferating cell nuclear antigen (PCNA)/cyclin. Bauer, G.A., Burgers, P.M. Biochim. Biophys. Acta (1988) [Pubmed]
  33. Isolation and characterization of cDNA clones encoding a functional p34cdc2 homologue from Zea mays. Colasanti, J., Tyers, M., Sundaresan, V. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  34. Proteolytic processing of Ty3 proteins is required for transposition. Kirchner, J., Sandmeyer, S. J. Virol. (1993) [Pubmed]
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