CYCLIN-A IS REQUIRED FOR THE ONSET OF DNA-REPLICATION IN MAMMALIAN FIBROBLASTS

Cyclin A protein is synthesized and localized into the nucleus at the onset of S phase in nontransformed mammalian fibroblasts. Inhibition of cyclin A synthesis or activity through microinjection of plasmids encoding antisense cyclin A cDNA or affinity-purified anti-cyclin A antibodies during G1 phase was shown to abolish the nuclear staining for cyclin A in plasmid-injected cells, and both procedures led to inhibition of DNA synthesis. No similar effect was observed with injection of other antisense vectors including antisense cyclin B, and reinjection of purified human cyclin A protein into cyclin A antisense-injected cells effectively relieved this inhibition of DNA synthesis. Taken together, these data suggest that cyclin A plays a major role in the control of DNA replication in mammalian cells.