Heinonen J, Joronen I, Tuokko H
Chem Biol Interact. 1976 Jan;12(1):91-8. doi: 10.1016/0009-2797(76)90070-3.
Hydroxyurea, an inhibitor of ribonucleoside diphosphate reductase, completely arrested the net synthesis of DNA for 3-4 h, when it was added in 30 mM concentration to growing cultures of Escherichia coli K12. Thereafter the net synthesis of DNA started again, although slowly, and simultaneously with it the formation of inorganic pyrophosphatase activity was stimulated leading to a 2-fold increase in the specific activity of the enzyme in 2-3 h. Subsequently cell division began again. In this way a new steady state, stable in the presence of hydroxyurea, was reached. This new state was characterized by the high specific activity of inorganic pyrophosphatase, a small but constant amount of DNA/cell mass (1/4 of the normal value), and large elongated cells. All these changes were slowly reversed during 5-6 h, when the cells were transferred into a drug-free medium. The activity of isoleucyl-tRNA synthetase, assayed as a control, did not change significantly in the presence of hydroxyurea. Hydroxyurea had no effect on the activity of inorganic pyrophosphatase in vitro.