Abstract
Although the enzymes of DNA precursor biosynthesis were originally described in the 1950s and 1960s, it is still timely to discuss these proteins with respect to their involvement in regulating DNA replication. This chapter will focus on current research that emphasizes the genetics and cell biology of these enzymes: How do the enzymes interact in cells, with each other, and with replication proteins? What controls reaction fluxes through individual enzymes in vivo? How do these fluxes vary through the cell cycle, and what factors control the variations? What are the effective concentrations of deoxyribonucleoside triphosphates (dNTPs*) at replication sites? How do variations in dNTP pools affect the rate and accuracy of DNA replication? What are the metabolic and genetic consequences of inhibiting a particular enzyme with an antimetabolite? Metabolic inhibitors provide useful probes for understanding compartmentation and control. In turn, this understanding could lead to the more effective use of antimetabolites as anticancer, antimicrobial, or antiviral agents.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Abbreviations
- rNMP, rNDP, rNTP:
-
ribonucleoside mono-, di-, and triphosphate, respectively
- dNMP, dNDP, dNTP:
-
deoxyribonucleoside mono-, di-, and triphosphate, respectively
References
Kornberg, A. (1989) DNA Replication, Third Edition; W.H. Freeman and Co., San Francisco (in press).
Eriksson, S., and Sjöberg, B.-M. (1988) CRC Crit. Rev. Biochem. (in press).
Eriksson, S., Gudas, L.J., Ullman, B., Clift, S.M., and Martin, D.W. Jr. (1981) J. Biol. Chem. 256, 10184–10189.
Reichard, P. (1988) Annu. Rev. Biochem. 57, 349–374.
McClarty, G.A., Chan, A.K., Engström, Y., Wright, J.A., and Thelander, L. (1987) Biochemistry 26, 8004–8011.
Weinberg, G., Ullman, B., and Martin, D.W. Jr. (1981) Proc. Natl. Acad. Sci. USA 78, 2447–2451.
Weinberg, G.L., Ullman, B., Wright, C.M., and Martin, D.W. Jr. (1985) Somat. Cell Mol. Genet. 11, 413–419.
Trudel, M., Van Genechten, T., and Meuth, M. (1984) J. Biol. Chem. 259, 2355–2359.
Aronow, B., Watts, T., Lasseter, J., Washtien, W., and Ullman, B. (1984) J. Biol. Chem. 259, 9035–9043.
Mathews, C.K. (1985) In Genetic Consequences of Nucleotide Pool Imbalance, De Serres, F.J., ed. Plenum Press, New York, pp. 47–66.
Dresler, S.L., Frattini, M.G., and Robinson-Hill, R. (1988) Biochemistry 27, 7247–7254.
Leeds, J.M., Slabaugh, M.B., and Mathews, C.K. (1985) Mol. Cell. Biol. 5, 3443–3450.
Bestwick, R.K., Moffett, G.L., and Mathews, C.K. (1982) J. Biol. Chem. 257, 9300–9304.
Mathews, C.K., and Sinha, N.K. (1982) Proc. Natl. Acad. Sci. USA 79, 302–306.
Mathews, C.K. (1976) Arch. Biochem. Biophys. 172, 178–187.
Moen, L.K., Howell, M.L., Lasser, G.W., and Mathews, C.K. (1988) J. Mol. Recog. 1, 48–57.
Flanegan, J.B., and Greenberg, G.R. (1977) J. Biol. Chem. 252, 3019–3027.
Chiu, C.-S., Cook, K.S., and Greenberg, G.R. (1982) J. Biol. Chem. 257, 15087–15097.
Wirak, D.O., Cook, K.S., and Greenberg, G.R. (1988) J. Biol. Chem. 263, 6193–6201.
Mathews, C.K., and Slabaugh, M.B. (1986) Exp. Cell Res. 162, 285–295.
Leeds, C.K., and Mathews, C.K. (1987) Mol. Cell. Biol. 7, 532–534.
Engström, Y., Rozell, H.-A., Stemme, S., and Thelander, L. (1984) EMBO J. 3, 863–867.
Kucera, R., and Paulus, H. (1986) Exp. Cell Res. 167, 417–423.
Vilpo, J.A., and Autio-Harmainen, H. (1983) Scand. J. Clin. Lab. Invest. 43, 583–587.
Wawra, E. (1988) J. Biol. Chem. 263, 9908–9912.
Reddy, C.K., and Mathews, C.K. (1978) J. Biol. Chem. 253, 3461–3467.
Pato, M.L. (1979) J. Bacteriol. 140, 518–524.
Manwaring, J.D., and Fuchs, J.A. (1979) J. Bacteriol. 138, 245–249.
Snyder, R.D. (1984) Mutat. Res. 131, 163–172.
Collins, A., and Oates, D.J. (1987) Eur. J. Biochem. 169, 299–305.
Scott, F.E., and Forsdyke, D.R. (1980) Biochem. J. 190, 721–730.
Nguyen, B.T., and Sadee, W. (1986) Biochem. J. 234, 263–269.
Nicander, B., and Reichard, P. (1982) Proc. Natl. Acad. Sci. USA 80, 1347–1351.
Lagergren, J., and Reichard, P. (1987) Biochem. J. 36, 2985–2991.
Slabaugh, M.B., Howell, M.L., Wang, Y., and Mathews, C.K. (in preparation).
Spyrou, G., and Reichard, P. (1987) J. Biol. Chem. 262, 16425–16432.
Bjursell, G., and Reichard, P. (1973) J. Biol. Chem. 248, 3904–3909.
Grindey, G.B., Winkler, M., Otten, M., and Steinberg, J.A. (1980) Mol. Pharmacol. 17, 256–261.
Steinberg, J.A., Otten, M., and Grindey, G.B. (1979) Cancer Res. 39, 4330–4335.
Wierowski, J.V., Lawton, K.G., Hockensmith, J.W., and Bambara, R.A. (1983) J. Biol. Chem. 258, 6250–6254.
Huberman, J.A. (1981) Cell 23, 647–648.
Nicander, B., and Reichard, P. (1981) Biochem. Biophys. Res. Commun. 210, 148–155.
Tan, C.-K., So, M.J., Downey, K.M., and So, A.G. (1987) Nucleic Acids Res. 14, 2269–2278.
Nicander, B., and Reichard, P. (1985) J. Biol. Chem. 260, 5376–5381.
Nicander, B., and Reichard, P. (1985) J. Biol. Chem. 260, 9216–9222.
Bianchi, V., Pontis, E., and Reichard, P. (1986) Proc. Natl. Acad. Sci. USA 83, 986–990.
Bianchi, V., Pontis, E., and Reichard, P. (1987) Mol. Cell. Biol. 7, 4218–4224.
Bianchi, V., Pontis, E., and Reichard, P. (1986) J. Biol. Chem. 261, 16037–16042.
Martin, D.W. Jr., and Gelfand, E.W. (1981) Annu. Rev. Biochem. 50, 845–877.
Seto, D., Bhatnagar, S.K., and Bessman, M.J. (1988) J. Biol. Chem. 263, 1494–1499.
Myers, J.A., Beauchamp, B.B., and Richardson, C.C. (1987) J. Biol. Chem. 262, 5288–5292.
Meuth, M. (1984) Mutat. Res. 126, 107–112.
DeSerres, F.J., ed. (1985) Genetic Consequences of Nucleotide Pool Imbalance. Plenum Press, New York.
Fersht, A.R. (1979) Proc. Natl. Acad. Sci. USA 76, 4946–4950.
Goncalves, O., Drobetsky, E., and Meuth, M. (1984) Mol. Cell. Biol. 4, 1792–1799.
Phear, G., Nalbantoglu, J., and Meuth, M. (1987) Proc. Natl. Acad. Sci. USA 84, 4450–4454.
Sargent, R.G., and Mathews, C.K. (1987) J. Biol. Chem. 262, 5546–5553.
Sargent, R.G., Mun, B.-J., and Mathews, C.K. (1989) Mol. Gen. Genet, in press.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1989 Springer-Verlag New York Inc.
About this chapter
Cite this chapter
Mathews, C.K. (1989). Enzymes of DNA Precursor Synthesis and the Control of DNA Replication. In: Adolph, K.W. (eds) Molecular Biology of Chromosome Function. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-3652-8_1
Download citation
DOI: https://doi.org/10.1007/978-1-4612-3652-8_1
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4612-8192-4
Online ISBN: 978-1-4612-3652-8
eBook Packages: Springer Book Archive