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 1 (10 μM) 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 1 (10 μM) had little effect on the first peak of the oscillation but reduced to less than half the second peak. These inhibitory effects of butyrolactone 1 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. © 1994 Academic Press. All rights reserved.