EVIDENCE FOR DOUBLE REPLICATION OF CHROMOSOMAL DNA SEGMENTS AS A GENERAL CONSEQUENCE OF DNA-REPLICATION INHIBITION

  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (6) , 2483-2490
Abstract
Evidence was previously presented 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. This effect is not a specific property of the ara-C molecule in that a similar effect is produced in cells [human retroorbital hemangioma Crow 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. Cycloheximide is an inhibitor of mammalian protein synthesis and inhibits DNA synthesis only indirectly, probably through a consequent deficiency of DNA-packaging proteins. 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.