Inhibiting a checkpoint (bottom) allows both early (green) and late (red) replication origins to fire.
When DNA replication goes awry, it is critical for a cell to detect and correct the error as soon as possible. Thus, when replication from an early-firing origin is blocked, an intra-S-phase checkpoint prevents the initiation of replication from late-firing origins. The molecular machinery of this checkpoint has remained poorly understood. Now, Feijoo et al. (page 913) describe the activities of the kinases Chk1 and Chk2 in mammalian cells during replication arrest, and demonstrate that Chk1 is required for this intra-S-phase checkpoint.
Arresting DNA replication in HeLa cells with hydroxyurea causes both Chk1 and Chk2 to be phosphorylated and activated, whereas neither protein is activated during normal S phase progression, suggesting that the proteins are phosphorylated in response to stalled or slowed replication. When the replication block is...
