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Gene Review

CDC8  -  bifunctional thymidylate/uridylate kinase

Saccharomyces cerevisiae S288c

Synonyms: J1715, Thymidylate kinase, YJR057W, dTMP kinase
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Disease relevance of CDC8

  • The gene is shown to be nonessential for the replication of vaccinia virus in cultured cells by the construction of a viable virus mutant that has the coding region of the TmpK gene interrupted by the Ecogpt gene [1].
  • Cell extracts of E. coli expressing the vaccinia gene contained high levels of TmpK activity, whereas extracts of cells without the TmpK gene did not [1].

High impact information on CDC8

  • Replication in vitro mimics that in vivo in that DNA synthesis in extracts of strain cdc8, a temperature-sensitive DNA replication mutant, is thermolabile relative to the wild-type, and in that aphidicolin inhibits replication in vitro [2].
  • Since the temperature-sensitive mutations are recessive, the products of genes cdc8 and cdc21 must be required for both nuclear and mitochondrial DNA replication [3].
  • Yeast 2-microns plasmid DNA replication in vitro: purification of the CDC8 gene product by complementation assay [4].
  • Seven of them fall into three complementation groups--cdc2, cdc8, and cdc16--involved in the control of the cell-division cycle [5].
  • Extracts prepared from the cell division cycle mutants cdc7 and cdc8, held in culture at the nonpermissive temperature, possessed diminished activity [6].

Chemical compound and disease context of CDC8


Biological context of CDC8


Anatomical context of CDC8


Associations of CDC8 with chemical compounds

  • The CDC8 gene of Saccharomyces cerevisiae encodes deoxythymidylate (dTMP) kinase and is required for nuclear and mitochondrial DNA replication in both the mitotic and meiotic cell cycles [14].
  • Unlike histone H2A mRNA, the CDC6 mRNA as well as CDC8 mRNA were not affected by hydroxyurea treatment [15].
  • The structures of TmpK with dTMP and with AZT-MP [Lavie, A., et al. (1997) Nat. Struct. Biol. 4, 601-604] implicate the movement of Arg15 in response to AZT-MP binding as an important factor in the 200-fold reduced catalytic rate with AZT-MP [7].
  • We propose that the resultant lysine to glutamate change stabilizes thermo-labile dTMP kinase molecules in the cell [14].
  • The interactions of TmpK and TP5A strongly suggest that arginine 15, which is located in the phosphate binding loop (P-loop) sequence, plays a catalytic role by interacting with an oxygen atom of the transferred phosphoryl group [7].

Regulatory relationships of CDC8

  • The CDC8 transcript is cell cycle regulated in yeast and is expressed coordinately with CDC9 and CDC21 at a point preceding histone transcription [16].
  • The SOE1 mutant contains a dominant suppressor that suppresses five different cdc8 alleles but does not suppress a complete cdc8 deletion [14].
  • The u.v.-sensitive rad4 mutant of yeast was found to decrease u.v.-induced reversion in the cdc8 and lys2 loci [17].

Other interactions of CDC8

  • The accumulation of CDC9 mRNA in late G1 is dependent upon the completion of start but not the CDC7 and CDC8 functions [18].
  • These data may explain an incomplete suppression of cdc8 by URA6, as previously observed [8].
  • POL1 (DNA polymerase I) and CDC8 (thymidylate kinase) transcription were unaltered, while histone H2B transcripts actually decreased by half [19].
  • This is precisely the same interval of the cell cycle in which three other yeast DNA synthesis genes, CDC8, CDC9 and CDC21, have been found to be periodically expressed (White et al 1987. Expl. Cell. Res., in press) [20].
  • This fragment lies 1 kilobase downstream from the well-characterized sup4 gene, a gene known to be genetically linked to CDC8, thus confirming that the cloned gene corresponds to the chromosomal CDC8 gene [21].


  1. Vaccinia virus encodes an active thymidylate kinase that complements a cdc8 mutant of Saccharomyces cerevisiae. Hughes, S.J., Johnston, L.H., de Carlos, A., Smith, G.L. J. Biol. Chem. (1991) [Pubmed]
  2. Yeast DNA replication in vitro: initiation and elongation events mimic in vivo processes. Celniker, S.E., Campbell, J.L. Cell (1982) [Pubmed]
  3. Mitochondrial DNA synthesis in cell cycle mutants of Saccharomyces cerevisiae. Newlon, C.S., Fangman, W.L. Cell (1975) [Pubmed]
  4. Yeast 2-microns plasmid DNA replication in vitro: purification of the CDC8 gene product by complementation assay. Arendes, J., Kim, K.C., Sugino, A. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  5. 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]
  6. Replication in vitro of the 2-micrometer DNA plasmid of yeast. Jazwinski, S.M., Edelman, G.M. Proc. Natl. Acad. Sci. U.S.A. (1979) [Pubmed]
  7. Crystal structure of yeast thymidylate kinase complexed with the bisubstrate inhibitor P1-(5'-adenosyl) P5-(5'-thymidyl) pentaphosphate (TP5A) at 2.0 A resolution: implications for catalysis and AZT activation. Lavie, A., Konrad, M., Brundiers, R., Goody, R.S., Schlichting, I., Reinstein, J. Biochemistry (1998) [Pubmed]
  8. Molecular characterization of Saccharomyces cerevisiae URA6 gene. DNA sequence, mutagenesis analysis, and cell cycle regulation relevant to its suppression mechanism to cdc8 mutation. Jiang, Z.R., Abaigar, L.T., Huang, S.H., Cai, B., Jong, A.Y. J. Biol. Chem. (1991) [Pubmed]
  9. Saccharomyces cerevisiae CDC8 gene and its product. Birkenmeyer, L.G., Hill, J.C., Dumas, L.B. Mol. Cell. Biol. (1984) [Pubmed]
  10. The CDC8 gene of yeast encodes thymidylate kinase. Jong, A.Y., Kuo, C.L., Campbell, J.L. J. Biol. Chem. (1984) [Pubmed]
  11. Analysis of a 42.5 kb DNA sequence of chromosome X reveals three tRNA genes and 14 new open reading frames including a gene most probably belonging to the family of ubiquitin-protein ligases. Huang, M.E., Chuat, J.C., Galibert, F. Yeast (1995) [Pubmed]
  12. Characterization of Saccharomyces cerevisiae thymidylate kinase, the CDC8 gene product. General properties, kinetic analysis, and subcellular localization. Jong, A.Y., Campbell, J.L. J. Biol. Chem. (1984) [Pubmed]
  13. Cell cycle inhibition of yeast spheroplasts. Murakami, S., Livingston, D.M. Mol. Gen. Genet. (1982) [Pubmed]
  14. Genetic and molecular analysis of the SOE1 gene: a tRNA(3Glu) missense suppressor of yeast cdc8 mutations. Su, J.Y., Belmont, L., Sclafani, R.A. Genetics (1990) [Pubmed]
  15. CDC6 mRNA fluctuates periodically in the yeast cell cycle. Zhou, C., Jong, A. J. Biol. Chem. (1990) [Pubmed]
  16. The CDC8 transcript is cell cycle regulated in yeast and is expressed coordinately with CDC9 and CDC21 at a point preceding histone transcription. White, J.H., Green, S.R., Barker, D.G., Dumas, L.B., Johnston, L.H. Exp. Cell Res. (1987) [Pubmed]
  17. Decreased u.v. mutagenesis in an excision-deficient mutant of yeast. Baranowska, H., Zaborowska, D., Zuk, J. Mutagenesis (1987) [Pubmed]
  18. Regulation of CDC9, the Saccharomyces cerevisiae gene that encodes DNA ligase. Peterson, T.A., Prakash, L., Prakash, S., Osley, M.A., Reed, S.I. Mol. Cell. Biol. (1985) [Pubmed]
  19. Deoxyribonucleotides are maintained at normal levels in a yeast thioredoxin mutant defective in DNA synthesis. Muller, E.G. J. Biol. Chem. (1994) [Pubmed]
  20. The yeast DNA polymerase I transcript is regulated in both the mitotic cell cycle and in meiosis and is also induced after DNA damage. Johnston, L.H., White, J.H., Johnson, A.L., Lucchini, G., Plevani, P. Nucleic Acids Res. (1987) [Pubmed]
  21. Cloning of Saccharomyces cerevisiae DNA replication genes: isolation of the CDC8 gene and two genes that compensate for the cdc8-1 mutation. Kuo, C.L., Campbell, J.L. Mol. Cell. Biol. (1983) [Pubmed]
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