EXPRESSION OF P60V-SRC IN SACCHAROMYCES-CEREVISIAE RESULTS IN ELEVATION OF P34CDC28 KINASE-ACTIVITY AND RELEASE OF THE DEPENDENCE OF DNA-REPLICATION ON MITOSIS

Expression of the oncogenic protein tyrosine kinase P60v-src in the ye ast Saccharomyces cerevisiae has been shown to result in rapid cell de ath (J. S. Brugge, G. Jarosik, J. Andersen, A- Queral-Lustig, M. Fedor -Chaiken, and J. R. Broach, Mol. Cell. Biol. 7:2180-2187, 1987). Work described here demonstrates that v-Src expression results in accumulat ion of large-budded cells and a nuclear division block without blockin g cytokinesis. Flow-cytometric analysis indicates that the DNA content of these cells is elevated beyond the G2 DNA content, and genetic stu dies indicate that v-Src expression causes aneuploidy. The activity of Cdc28 kinase, which controls the G1/S and G2/M transitions in S. cere visiae, increases during galactose induction in a Src+ strain but not in an isogenic Src- strain. These observations indicate that v-Src exp ression disrupts p3P34CDC28 kinase regulation, allowing DNA replicatio n to proceed in the absence of a prior mitotic event.