Cdc18 transcription and proteolysis couple S phase to passage through mitosis

In fission yeast, cdc18p plays a critical role in bringing about the onset of S phase. We show that cdc18p expression is subject to a complex sequence of cell cycle controls which ensure that cdc18p levels rise dramatically as cells exit mitosis, before the appearance of CDK activity in G1. We find that transcription of cdc18, together with the transcription of other cdc10p/res1p targets, is first initiated as cells enter mitosis and continues even in cells arrested in mitosis with highly condensed chromatin. However, cdc18p cannot accumulate during mitosis because it is targeted for proteolysis by mitotic cdc2p-protein kinase-mediated phosphorylation. On exit from mitosis, the cdc2p mitotic kinase activity falls, stabilizing cdc18p, which then rapidly accumulates. This combination of mitotic transcription and CDK-mediated proteolysis ensures that progression through mitosis simultaneously prepares cells for DNA replication. During S phase, cdc18 transcription is then switched off, preventing the re-initiation of DNA synthesis until the completion of the next round of mitosis.