Evidence for double replication of chromosomal DNA segments as a general consequence of DNA replication inhibition.
We have previously presented evidence that a transient inhibition of DNA synthesis by a pulse of 1-beta-D-arabinofuranosylcytosine (ara-C) results in a disruption of the pattern of replication of the chromosomal DNA of cultured human cells, resulting in some DNA segments being replicated more than once in a single S phase. Further evidence is presented in this paper that this effect is not a specific property of the ara-C molecule in that a similar effect is produced in cells by a pulse of 9-beta-D-arabinofuranosyladenine (ara-A) and also by a pulse of cycloheximide. The activated form of ara-A and ara-C (the triphosphates) both inhibit DNA synthesis at the level of the polymerase. Double replication following an ara-A pulse demonstrates that double replication after an ara-C pulse is not caused by some specific property of the ara-C molecule which might be unrelated to any effect on DNA synthesis. However, cycloheximide is an inhibitor of mammalian protein synthesis and inhibits DNA synthesis only indirectly, probably through a consequent deficiency of DNA-packaging proteins. Hence, the occurrence of double replication of chromosomal DNA segments following a pulse of cycloheximide is consistent with this phenomenon being a general and nonspecific consequence of the freezing of DNA replication forks.
D002460:Cell Line; D002869:Chromosome Aberrations; D003513:Cycloheximide / Q000494:pharmacology*; D003561:Cytarabine / Q000494:pharmacology; D004260:DNA Repair; D004261:DNA Replication / Q000187:drug effects*; D004259:DNA-Directed DNA Polymerase; D006801:Humans; D007399:Interphase; D014740:Vidarabine / Q000494:pharmacology*
D003561:Cytarabine; D003513:Cycloheximide; D004259:DNA-Directed DNA Polymerase; D014740:Vidarabine