Inhibition of cell cycle oscillation of DNA replication by a selective inhibitor of the cdc2 kinase family, butyrolactone I, in Xenopus egg extracts.

A selective inhibitor of the cdc2 kinase family, butyrolactone I, was found to inhibit the DNA replication activity of Xenopus egg extracts. When metaphase-arrested Xenopus egg extracts pretreated with butyrolactone I were released into interphase by the addition of CaCl2 at low concentrations of sperm nuclei, butyrolactone I (10 microM) prevented the oscillation of DNA replication activity to a great extent and lengthened the cell cycle. In contrast, in activated extracts which had already entered interphase, prepared from eggs activated by the calcium ionophore A23187, butyrolactone I (10 microM) had little effect on the first peak of the oscillation but reduced to less than half the second peak. These inhibitory effects of butyrolactone I on the initiation of DNA replication and mitosis in Xenopus egg extracts are probably a consequence of its previously reported inhibition of the cyclin-cdc2 kinase family.