CDC18 TRANSCRIPTION AND PROTEOLYSIS COUPLE S-PHASE TO PASSAGE THROUGHMITOSIS

In fission yeast, cdc18p plays a critical role in bringing about the o nset of S phase. We show that cdc18p expression is subject to a comple x sequence of cell cycle controls which ensure that cdc18p levels rise dramatically as cells exit mitosis, before the appearance of CDK acti vity in G(1). We find that transcription of cdc18, together with the t ranscription of other cdc10p/res1p targets, is first initiated as cell s enter mitosis and continues even in cells arrested in mitosis with h ighly condensed chromatin, However, cdc18p cannot accumulate during mi tosis because it is targeted for proteolysis by mitotic cdc2p-protein kinase-mediated phosphorylation. On exit from mitosis, the cdc2p mitot ic kinase activity falls, stabilizing cdc18p, which then rapidly accum ulates. This combination of mitotic transcription and CDK-mediated pro teolysis ensures that progression through mitosis simultaneously prepa res cells for DNA replication. During S phase, cdc18 transcription is then switched off, preventing the reinitiation of DNA synthesis until the completion of the next round of mitosis.