S-Phase Damage-Sensing Checkpoints

Definition

Cell cycle checkpoints function by sensing DNA damage and transmitting a signal that results in arrest at defined stages of the cycle. The S phase “checkpoint” halts cells during the DNA synthetic period in response to DNA damage (DNA damage responses) and is somewhat different from other checkpoints in two ways. First, in the classic paradigm, cell cycle progression is halted at various discrete points in the cycle (e.g., in G₁, at the G₂/M transition, and during mitosis), and cells are usually arrested for many hours prior to reentry into the cycle. In contrast, the S phase damage-sensing pathway arrests cell cycle progression for only an hour or so and seemingly at any position within the S phase; therefore, it is difficult to think of it as a checkpoint per se (although we will refer to it as such in this review). As more is learned about the molecular basis of all of the checkpoints, it is becoming clear that each may have multiple targets. Thus, the underlying...