Evidence for the resumption of DNA replication prior to histone synthesis in HeLa cells after release from treatment with hydroxyurea

Hydroxyurea, which brings about a rapid but reversible inhibition of DNA replication and histone synthesis in HeLa cells [l-7], has provided valuable information regarding the relationship between these metabolic events. Although time course and biochemical changes associated with inhibition have been extensively examined [l-7], little is known regarding the release from the metabolic block imposed by hydroxyurea. Because of the potential value of this inhibitor for further assessing the apparent functional coupling of DNA replication and histone synthesis, we have examined histone and DNA synthesis at various times after removal of hydroxyurea from HeLa cell cultures. These results indicate that the resumption of DNA synthesis precedes that of histone synthesis.