DNA checkpoints in fission yeast.

The DNA integrity checkpoints ensure completion of DNA replication and DNA repair before entry into mitosis (O’Connell et al., 2000). Unreplicated DNA or unrepaired DNA will cause catastrophic chromosome segregation. The accompanying schematic shows the checkpoint proteins that monitor the state of DNA replication and DNA repair. Checkpoint proteins most probably interact with the replication complex (RC) during S phase (blue wedge) or with DNA strand breaks if they are induced during G2 phase (yellow wedge). These checkpoint proteins ultimately inactivate the Cdc2–cyclin-B kinase complex by inhibitory Tyr15 phosphorylation (O’Connell et al., 2000). High Cdc2–cyclin-B kinase activity allows the cell to enter mitosis (pink wedge), where chromosome separation and segregation occur (see bottom left, upper panel). Checkpoint activation thus causes cell cycle arrest in G2 phase (see bottom left, lower panel). Evolutionary conserved checkpoint proteins (see table) have been classified into several categories, including the ATR-ATRIP kinase complex (Rad3Rad26), the RFCand PCNA-like complexes (Rad1, Rad9, Hus1 and Rad17), the mediator proteins (Crb2 and Mrc1) and the effector kinases (Chk1 and Cds1).