Abstract
Thymidylate synthase (TS) catalyzes the reductive methylation of dUMP to form TMP in the de novo biosynthetic pathway. The enzyme is essential in proliferating cells and is an important target for a variety of cancer chemotherapeutic drugs (Danenberg, 1977). The TS gene is expressed at a very low level in non-proliferating cells. When the quiescent cells are stimulated to proliferate, the amount of TS mRNA and enzyme remain low during G1 phase, then increase 10–20 fold as the cells progress through S phase (Navalgund et al., 1980).
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References
Ash, J., Ke, Y., Korb, M., and Johnson, L.F., 1993, Introns are essential for growth-regulated expression of the mouse thymidylate synthase gene. Mol. Cell. Biol. 13: 1565–15710.
Ayusawa, D., Shimizu, K., Koyama, H., Kaneda, S., Takeishi, K., and Seno, T., 1986, Cell-cycle-directed regulation of thymidylate synthase messenger RNA in human diploid fibroblasts stimulated to proliferate. J. Mol. Biol. 190: 559–567.
Danenberg, P.V., 1977, Thymidylate synthetase — a target enzyme in cancer chemotherapy. Biochim. Biophys. Acta 473: 73–92.
Deng, T., Li, D., Jente, C.-H., and Johnson, L.F., 1986, Structure of the gene for mouse thymidylate synthase: Locations of introns and multiple transcriptional start sites. J. Biol. Chem. 261: 16000–16005.
Deng, T., Li, Y., Jolliff, K., and Johnson, L.F., 1989, The mouse thymidylate synthase promoter: essential elements are in close proximity to the transcriptional inititation sites. Mol. Cell. Biol. 9: 4079–4082.
Geng, Y., and Johnson, L.F., 1993, Lack of an initiator element is responsible for multiple transcriptional initiation sites of the TATA-less mouse thymidylate synthase promoter. Mol. Cell. Biol. 13: 4894–4903.
Jente, C.-H., Geyer, P.K., and Johnson, L.F., 1985, Control of thymidylate synthase mRNA content and gene transcription in an overproducing mouse cell line. Mol. Cell. Biol. 5: 2527–2532.
Johnson, L.F., 1992, G1 events and the regulation of genes for S-phase enzymes. Curr. Opin. Cell Biol. 4: 149–154.
Jolliff, K., Li, Y., and Johnson, L.F., 1991, Multiple protein-DNA interactions in the TATAA-less mouse thymidylate synthase promoter. Nucleic Acids Res. 19: 2267–2274.
Kaneda, S., Takeishi, K., Ayusawa, D., Shimizu, K., Seno, T., and Altman, S., 1987, Role in translation of a triple tandemly repeated sequence in the 5′-untranslated region of human thymidylate synthase mRNA. Nucleic Acids Res. 15: 1259–1270.
Kaneda, S., Nalbantoglu, J., Takeishi, K., Shimizu, K., Gotoh, O., Seno, T., and Ayusawa, D., 1990, Structural and functional analysis of the human thymidylate synthase gene. J. Biol. Chem. 265: 20277–20284.
Li, Y., Li, D., Osborn, K., and Johnson, L.F., 1991, The 5′ flanking region of the mouse thymidylate synthase gene is necessary but not sufficient for normal regulation in growth-stimulated cells. Mol. Cell. Biol. 11: 1023–1029.
Navalgund, L.G., Rossana, C., Muench, A.J., and Johnson, L.F., 1980, Cell cycle regulation of thymidylate synthetase gene expression in cultured mouse fibroblasts. J. Biol. Chem. 255: 7386–7390.
Perryman, S.M., Rossana, C., Deng, T., Vanin, E.F., and Johnson, L.F., 1986, Sequence of a cDNA for mouse thymidylate synthase reveals striking similarity with the prokaryotic enzyme. Mol. Biol. Evol. 3: 313–321.
Takeishi, K., Kaneda, S., Ayusawa, D., Shimizu, K., Gotoh, O., and Seno, T., 1985, Nucleotide sequence of a functional cDNA for human thymidylate synthase. Nucleic Acids Res. 13: 2035–2043.
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© 1994 Springer Science+Business Media New York
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Johnson, L.F. (1994). Regulation of Thymidylate Synthase Gene Expression in Growth-Stimulated Cells. In: Hu, V.W. (eds) The Cell Cycle. GWUMC Department of Biochemistry Annual Spring Symposia. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2421-2_15
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DOI: https://doi.org/10.1007/978-1-4615-2421-2_15
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