Thymine deficiency and the normal DNA replication cycle. I

In the absence of thymine, bacterial strains that require this compound for growth lose viability in a characteristic manner. If, at the time when thymine is removed from a culture, protein and RNA synthesis are inhibited a small fraction of the cells is found to be immune to thymineless death. Under conditions of in- hibited protein and RNA synthesis total DNA is found to increase by 40% or more. During this period of DNA synthesis the entire cell population gradually becomes immune; i.e. reaches a state in which subsequent removal of thymine does not cause death. To account for these observations we postulate that protein and/or RNA synthesis is necessary to initiate but not to sustain DNA replication. During renewed growth the acquired immunity to thymineless death is gradually lost and, in parallel, DNA synthesis is resumed. The steps by which a new DNA replication cycle is initiated require protein and/or RNA synthesis but take place as efficiently in the presence as in the absence of thymine. The chemical nature of these steps is unknown, but they are clearly independent of the replica- tion process proper.