Figure 1. Checkpoint activation and regulation of the replisome complex. (A) The replication checkpoint in fission yeast. Replication stress activates the Rad3-dependent checkpoint pathway, which is mediated by Mrc1 and the Swi1-Swi3 FPC. Rad3 sends a checkpoint signal to downstream checkpoint effector Cds1 to arrest the cell cycle and facilitate DNA repair pathways. Functional human homologs are indicated in parentheses. (B) SCFPof3-dependent replisome ubiquitination in response to replication stress. Natural impediments generate replication stress that activates SCFPof3 and ubiquitinates several replisome components for degradation. Replication stress also causes RPA accumulation, leading to checkpoint activation.