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Gene Review

CDC21  -  thymidylate synthase

Saccharomyces cerevisiae S288c

Synonyms: CRT9, Cell division cycle protein 21, Constitutive RNR3 transcription protein 9, TMP1, TS, ...
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Disease relevance of CDC21


High impact information on CDC21

  • Since the temperature-sensitive mutations are recessive, the products of genes cdc8 and cdc21 must be required for both nuclear and mitochondrial DNA replication [5].
  • MCBs are both necessary and sufficient for the late G1-specific transcription of the TMP1 thymidylate synthase and POL1 DNA polymerase genes [6].
  • We describe here the formation in vitro of complexes on TMP1 MCBs that contain the Swi6 protein and, we suggest, a protein of relative molecular mass 120,000 (p120) that is distinct from Swi4 [6].
  • We have applied this method to the DNA replication factor mcm4/cdc21, and find that chromatin association occurs during anaphase B, significantly earlier than is the case in budding yeast [7].
  • This sequence has been shown to be essential for periodic expression of the POL1, CDC9, and TMP1 genes [8].

Biological context of CDC21

  • The timing of this event was compared with those of CDC9 and CDC21, which are already known to be periodically transcribed, and all three genes were found to be expressed at the same time in the cell cycle [9].
  • By also deleting the gene encoding thymidylate synthase (CDC21) we have constructed strains that are entirely dependent upon exogenous thymidine for viability and that can grow with normal kinetics at low thymidine concentrations [10].
  • In cdc8 and cdc21, mutants defective in continued replication during the S phase of the cell cycle, mitochondrial DNA replication ceases at the nonpermissive temperature [5].
  • The deduced amino acid sequence is similar to TS from other organisms and is most closely related to the enzyme from Saccharomyces cerevisiae with 65% identity [1].
  • TS is found on a 330-kilobase-pair chromosome in P. carinii [1].

Associations of CDC21 with chemical compounds


Regulatory relationships of CDC21

  • Our findings indicate that the relative expression levels of both dUTPase and uracil-DNA glycosylase can have great influence over the efficacy of thymidylate synthase-directed chemotherapy, thereby enhancing the candidacy of these proteins as prognostic markers and alternative targets for therapeutic development [13].

Other interactions of CDC21


Analytical, diagnostic and therapeutic context of CDC21


  1. Isolation and expression of the Pneumocystis carinii thymidylate synthase gene. Edman, U., Edman, J.C., Lundgren, B., Santi, D.V. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  2. Molecular characterization of the cell cycle-regulated thymidylate synthase gene of Saccharomyces cerevisiae. Taylor, G.R., Lagosky, P.A., Storms, R.K., Haynes, R.H. J. Biol. Chem. (1987) [Pubmed]
  3. Identification of a thymidylate synthase gene within the genome of Chilo iridescent virus. Müller, K., Tidona, C.A., Bahr, U., Darai, G. Virus Genes (1998) [Pubmed]
  4. Pteroyl- and tetrahydropteroylpolyglutamate effects on the catalytic activity of thymidylate synthase from Lactobacillus leichmannii: a novel method for determining gamma-glutamyl chain lengths of the folylpolyglutamates. Rao, K.N. Indian J. Biochem. Biophys. (1994) [Pubmed]
  5. Mitochondrial DNA synthesis in cell cycle mutants of Saccharomyces cerevisiae. Newlon, C.S., Fangman, W.L. Cell (1975) [Pubmed]
  6. 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]
  7. Chromatin binding of the fission yeast replication factor mcm4 occurs during anaphase and requires ORC and cdc18. Kearsey, S.E., Montgomery, S., Labib, K., Lindner, K. EMBO J. (2000) [Pubmed]
  8. Regulation of the yeast DNA replication genes through the Mlu I cell cycle box is dependent on SWI6. Verma, R., Smiley, J., Andrews, B., Campbell, J.L. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  9. 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]
  10. Reconstitution of an efficient thymidine salvage pathway in Saccharomyces cerevisiae. Vernis, L., Piskur, J., Diffley, J.F. Nucleic Acids Res. (2003) [Pubmed]
  11. Limited TTP supply affects telomere length regulation in a telomerase-independent fashion. Toussaint, M., Dionne, I., Wellinger, R.J. Nucleic Acids Res. (2005) [Pubmed]
  12. A proposed clinical test for monitoring fluoropyrimidine therapy: detection and stability of thymidylate synthase ternary complexes. Brody, J.R., Gallmeier, E., Yoshimura, K., Hucl, T., Kulesza, P., Canto, M.I., Hruban, R.H., Schulick, R.D., Kern, S.E. Cancer Biol. Ther. (2006) [Pubmed]
  13. dUTPase and uracil-DNA glycosylase are central modulators of antifolate toxicity in Saccharomyces cerevisiae. Tinkelenberg, B.A., Hansbury, M.J., Ladner, R.D. Cancer Res. (2002) [Pubmed]
  14. Identification and purification of a factor that binds to the Mlu I cell cycle box of yeast DNA replication genes. Verma, R., Patapoutian, A., Gordon, C.B., Campbell, J.L. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  15. Cdc54 belongs to the Cdc46/Mcm3 family of proteins which are essential for initiation of eukaryotic DNA replication. Whitebread, L.A., Dalton, S. Gene (1995) [Pubmed]
  16. Meiosis-specific regulation of the Saccharomyces cerevisiae S-phase cyclin CLB5 is dependent on MluI cell cycle box (MCB) elements in its promoter but is independent of MCB-binding factor activity. Raithatha, S.A., Stuart, D.T. Genetics (2005) [Pubmed]
  17. Thioredoxin reductase-dependent inhibition of MCB cell cycle box activity in Saccharomyces cerevisiae. Machado, A.K., Morgan, B.A., Merrill, G.F. J. Biol. Chem. (1997) [Pubmed]
  18. Thymidylate synthase is localized to the nuclear periphery in the yeast Saccharomyces cerevisiae. Poon, P.P., Storms, R.K. J. Biol. Chem. (1994) [Pubmed]
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