The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Chemical Compound Review

T9758_SIGMA     [3-hydroxy-5-(5-methyl-2,4- dioxo-pyrimidin...

Synonyms: NSC-46713, KST-1B3754, AC1L1ATB, AC1Q6RZH, NSC46713, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of deoxythymidylate

  • Characterization of the intron in the phage T4 thymidylate synthase gene and evidence for its self-excision from the primary transcript [1].
  • The interrupted T4 phage td gene, which encodes thymidylate synthase, is the first known example of an intron-containing prokaryotic structural gene [2].
  • Structure of large fragment of Escherichia coli DNA polymerase I complexed with dTMP [3].
  • The fragile site at Xq27, associated with a common form of X-linked mental retardation (XLMR), is expressed in a variable proportion of the peripheral lymphocytes of affected males when the cells are cultured under thymidylate stress (Td stress) produced by folate or thymidylate deprivation [4].
  • The atomic structure of thymidylate synthase from Lactobacillus casei was determined at 3 angstrom resolution [5].

Psychiatry related information on deoxythymidylate

  • It is induced in culture by conditions of thymidylate stress and is generally considered a rare fragile site found only in association with an X-linked form of mental retardation [6].

High impact information on deoxythymidylate


Chemical compound and disease context of deoxythymidylate

  • Bacteriophage T4 deoxynucleotide kinase (DNK) is the only member of this family of enzymes that recognizes three structurally dissimilar nucleotides: dGMP, dTMP and 5-hydroxymethyl-dCMP while excluding dCMP and dAMP [10].
  • With these mutants the rate of increase of dTMP synthetase and dCMP hydroxymethylase activities was always substantially lower than after infection by wild-type phage [11].
  • However, previous studies of impaired DNA synthesis and repair in megaloblastic anemia have concerned mainly the decreased intracellular levels of thymidylate and its effects on nucleotide pools and misincorporation of uracil into DNA [12].
  • Efforts to use fresh human sarcoma cells for evaluating antifolate resistance with an in situ thymidylate synthesis assay using 5-[3H] deoxyuridine were unsuccessful because of low thymidylate synthesis activity in enzymatically disaggregated tumors [13].
  • The binding of 5-fluorodeoxyuridylate (FdUMP) to carboxypeptidase-inactivated thymidylate synthase obtained from methotrexate-resistant Lactobacillus casei was investigated using [3H]FdUMP in a trichloroacetic acid precipitation assay and by 19F nuclear magnetic resonance spectroscopy [14].

Biological context of deoxythymidylate


Anatomical context of deoxythymidylate

  • MTX sensitivity in patient-derived cell lines of SCLC requires the ability of cells to accumulate and retain intracellular drug in the form of polyglutamate metabolites in excess of dihydrofolate reductase, as well as a high basal level of consumption of reduced folates in the synthesis of thymidylate [19].
  • De novo synthesis of a polymer of deoxyadenylate and deoxythymidylate by calf thymus DNA polymerase alpha [20].
  • Using a somatic cell hybrid system, we previously demonstrated that fragile-X expression can be induced by thymidylate stress in normal X chromosomes at low levels (4%-5%) [6].
  • We also investigated the import and export of thymidine phosphates in mouse liver mitochondria and provide evidence for a rapid, highly selective, and saturable import of dTMP, not depending on a functional respiratory chain [21].
  • FdUrd also was metabolized by bone marrow cells, produced a low level of FUra incorporation into RNA (0.23 pmol FUra per micrograms RNA at 2 hr), and produced a complete inhibition of thymidylate synthetase activity [22].

Associations of deoxythymidylate with other chemical compounds


Gene context of deoxythymidylate

  • MCBs are both necessary and sufficient for the late G1-specific transcription of the TMP1 thymidylate synthase and POL1 DNA polymerase genes [28].
  • The production of excess thymidylate by a virus thymidylate synthase in cells infected with an A+T-rich herpesvirus would provide one plausible source of biased mutations by the virus-encoded replicative enzymes, which we have previously suggested as the likely general cause of differences in the mean nucleotide compositions of herpesvirus genomes [29].
  • Despite the role of dCMP deaminase in dTTP biosynthesis, Northern analysis revealed that the DCD1 gene is not subject to the same cell cycle-dependent pattern of transcription recently found for the yeast thymidylate synthetase gene (TMP1) [30].
  • Since CDC8 encodes thymidylate kinase, cells bearing a high copy number plasmid containing SOC8-1 gene were tested for the ability to phosphorylate several nucleoside monophosphates, including UMP, GMP and dTMP [31].
  • 5' to dfrA is a thymidylate synthetase gene, designated thyE [32].

Analytical, diagnostic and therapeutic context of deoxythymidylate


  1. Characterization of the intron in the phage T4 thymidylate synthase gene and evidence for its self-excision from the primary transcript. Chu, F.K., Maley, G.F., West, D.K., Belfort, M., Maley, F. Cell (1986) [Pubmed]
  2. Processing of the intron-containing thymidylate synthase (td) gene of phage T4 is at the RNA level. Belfort, M., Pedersen-Lane, J., West, D., Ehrenman, K., Maley, G., Chu, F., Maley, F. Cell (1985) [Pubmed]
  3. Structure of large fragment of Escherichia coli DNA polymerase I complexed with dTMP. Ollis, D.L., Brick, P., Hamlin, R., Xuong, N.G., Steitz, T.A. Nature (1985) [Pubmed]
  4. Implications of fragile X expression in normal males for the nature of the mutation. Ledbetter, D.H., Ledbetter, S.A., Nussbaum, R.L. Nature (1986) [Pubmed]
  5. Atomic structure of thymidylate synthase: target for rational drug design. Hardy, L.W., Finer-Moore, J.S., Montfort, W.R., Jones, M.O., Santi, D.V., Stroud, R.M. Science (1987) [Pubmed]
  6. A common fragile site at Xq27: theoretical and practical implications. Ledbetter, S.A., Ledbetter, D.H. Am. J. Hum. Genet. (1988) [Pubmed]
  7. The catalytic mechanism and structure of thymidylate synthase. Carreras, C.W., Santi, D.V. Annu. Rev. Biochem. (1995) [Pubmed]
  8. Folate-induced remission in aplastic anemia with familial defect of cellular folate uptake. Branda, R.F., Moldow, C.F., MacArthur, J.R., Wintrobe, M.M., Anthony, B.K., Jacob, H.S. N. Engl. J. Med. (1978) [Pubmed]
  9. The bottleneck in AZT activation. Lavie, A., Schlichting, I., Vetter, I.R., Konrad, M., Reinstein, J., Goody, R.S. Nat. Med. (1997) [Pubmed]
  10. Crystal structure of bacteriophage T4 deoxynucleotide kinase with its substrates dGMP and ATP. Teplyakov, A., Sebastiao, P., Obmolova, G., Perrakis, A., Brush, G.S., Bessman, M.J., Wilson, K.S. EMBO J. (1996) [Pubmed]
  11. Simultaneous initiation of synthesis of bacteriophage T4 DNA and of deoxyribonucleotides. Chiu, C.S., Tomich, P.K., Greenberg, G.R. Proc. Natl. Acad. Sci. U.S.A. (1976) [Pubmed]
  12. Apoptosis in megaloblastic anemia occurs during DNA synthesis by a p53-independent, nucleoside-reversible mechanism. Koury, M.J., Price, J.O., Hicks, G.G. Blood (2000) [Pubmed]
  13. Mechanisms of natural resistance to antifolates in human soft tissue sarcomas. Li, W.W., Lin, J.T., Tong, W.P., Trippett, T.M., Brennan, M.F., Bertino, J.R. Cancer Res. (1992) [Pubmed]
  14. Studies of 5-fluorodeoxyuridine 5'-monophosphate binding to carboxypeptidase A-inactivated thymidylate synthase from Lactobacillus casei. Cisneros, R.J., Zapf, J.W., Dunlap, R.B. J. Biol. Chem. (1993) [Pubmed]
  15. dUTP pyrophosphatase is an essential enzyme in Saccharomyces cerevisiae. Gadsden, M.H., McIntosh, E.M., Game, J.C., Wilson, P.J., Haynes, R.H. EMBO J. (1993) [Pubmed]
  16. Crystal structure of deoxycytidylate hydroxymethylase from bacteriophage T4, a component of the deoxyribonucleoside triphosphate-synthesizing complex. Song, H.K., Sohn, S.H., Suh, S.W. EMBO J. (1999) [Pubmed]
  17. An intron in the thymidylate synthase gene of Bacillus bacteriophage beta 22: evidence for independent evolution of a gene, its group I intron, and the intron open reading frame. Bechhofer, D.H., Hue, K.K., Shub, D.A. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  18. Crystal structure of a human mitochondrial deoxyribonucleotidase. Rinaldo-Matthis, A., Rampazzo, C., Reichard, P., Bianchi, V., Nordlund, P. Nat. Struct. Biol. (2002) [Pubmed]
  19. Determinants of the sensitivity of human small-cell lung cancer cell lines to methotrexate. Curt, G.A., Jolivet, J., Carney, D.N., Bailey, B.D., Drake, J.C., Clendeninn, N.J., Chabner, B.A. J. Clin. Invest. (1985) [Pubmed]
  20. De novo synthesis of a polymer of deoxyadenylate and deoxythymidylate by calf thymus DNA polymerase alpha. Henner, D., Furth, J.J. Proc. Natl. Acad. Sci. U.S.A. (1975) [Pubmed]
  21. Mitochondrial deoxynucleotide pool sizes in mouse liver and evidence for a transport mechanism for thymidine monophosphate. Ferraro, P., Nicolosi, L., Bernardi, P., Reichard, P., Bianchi, V. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  22. Selective activation of 5'-deoxy-5-fluorouridine by tumor cells as a basis for an improved therapeutic index. Armstrong, R.D., Diasio, R.B. Cancer Res. (1981) [Pubmed]
  23. Biochemical modulation of 5-bromo-2'-deoxyuridine and 5-iodo-2'-deoxyuridine incorporation into DNA in VX2 tumor-bearing rabbits. Stetson, P.L., Normolle, D.P., Knol, J.A., Johnson, N.J., Yang, Z.M., Sakmar, E., Prieskorn, D., Terrio, P., Knutsen, C.A., Ensminger, W.D. J. Natl. Cancer Inst. (1991) [Pubmed]
  24. Molecular complementation of a genetic marker in Dictyostelium using a genomic DNA library. Dynes, J.L., Firtel, R.A. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  25. Accumulation of DNA strand breaks and methotrexate cytotoxicity. Li, J.C., Kaminskas, E. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  26. Kinetic measurement of 2-aminopurine X cytosine and 2-aminopurine X thymine base pairs as a test of DNA polymerase fidelity mechanisms. Watanabe, S.M., Goodman, M.F. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  27. Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: implications for cancer and neuronal damage. Blount, B.C., Mack, M.M., Wehr, C.M., MacGregor, J.T., Hiatt, R.A., Wang, G., Wickramasinghe, S.N., Everson, R.B., Ames, B.N. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  28. 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]
  29. The A+T-rich genome of Herpesvirus saimiri contains a highly conserved gene for thymidylate synthase. Honess, R.W., Bodemer, W., Cameron, K.R., Niller, H.H., Fleckenstein, B., Randall, R.E. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  30. Sequence and expression of the dCMP deaminase gene (DCD1) of Saccharomyces cerevisiae. McIntosh, E.M., Haynes, R.H. Mol. Cell. Biol. (1986) [Pubmed]
  31. The Saccharomyces cerevisiae SOC8-1 gene and its relationship to a nucleotide kinase. Choi, W.J., Campbell, J.L., Kuo, C.L., Jong, A.Y. J. Biol. Chem. (1989) [Pubmed]
  32. Trimethoprim resistance transposon Tn4003 from Staphylococcus aureus encodes genes for a dihydrofolate reductase and thymidylate synthetase flanked by three copies of IS257. Rouch, D.A., Messerotti, L.J., Loo, L.S., Jackson, C.A., Skurray, R.A. Mol. Microbiol. (1989) [Pubmed]
  33. Intervening sequence in the thymidylate synthase gene of bacteriophage T4. Chu, F.K., Maley, G.F., Maley, F., Belfort, M. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  34. Induction, by thymidylate stress, of genetic recombination as evidenced by deletion of a transferred genetic marker in mouse FM3A cells. Ayusawa, D., Koyama, H., Shimizu, K., Kaneda, S., Takeishi, K., Seno, T. Mol. Cell. Biol. (1986) [Pubmed]
  35. Effect of methotrexate on thymidylate synthetase in cultured parenchymal cells isolated from regenerating rat liver. Bonney, R.J., Maley, F. Cancer Res. (1975) [Pubmed]
  36. Mimosine targets serine hydroxymethyltransferase. Lin, H.B., Falchetto, R., Mosca, P.J., Shabanowitz, J., Hunt, D.F., Hamlin, J.L. J. Biol. Chem. (1996) [Pubmed]
  37. Purification of mammalian tumor (L1210) thymidylate synthetase by affinity chromatography on stable biospecific adsorbent. Stabilization of the enzyme with neutral detergents. Rode, W., Scanlon, K.J., Hynes, J., Bertino, J.R. J. Biol. Chem. (1979) [Pubmed]
WikiGenes - Universities