Histone synthesis in Leishmania infantum is tightly linked to DNA replication by a translational control

We have analysed the regulation of histone synthesis in Leishmania infantum following inhibition of DNA replication. Run-on experiments indicated that transcription rates of the genes coding for the four core histones (H2A, H 2B, H3 and H4) were not affected by the inhibition with hydroxyurea of DNA synthesis. However, a dramatic decrease was observed in the newly synthesiz ed histones after inhibition of DNA synthesis. Furthermore, the synthesis o f both the histones and DNA resumed in promastigotes after removal of hydro xyurea, indicating that inhibition was reversible. Unlike most eukaryotes, in which the replication-dependent histone transcripts decrease upon a repl ication blockade, the levels of L. infantum histone mRNAs do not change und er similar conditions. Thus the present data indicate that histone synthesi s in Leishmania is tightly coupled to DNA replication by a mechanism operat ing at the translational level.