Checkpoint Pathways Establish Dependencies and Prevent Errors in the Cell Cycle

The experiments that led to the idea of surveillance mechanisms or checkpoint pathways establishing dependencies in the cell cycle were simple and beautiful in their interpretation (see Classic Experiment 19-3). Recall that Lee Hartwell and colleagues isolated temperature-sensitive cdc mutants in S. cerevisiae. It was the characterization of one of these cdc mutants that led Hartwell and colleagues to formulate the checkpoint pathway concept: a checkpoint pathway ensures that a cell cycle phase does not commence before the previous one has been completed. In addition to establishing dependencies, the checkpoint pathways ensure that each aspect of chromosome replication and division occurs with accuracy.

Today we know that cells harbor multiple checkpoint pathways and that each is built in the same manner. A sensor detects a defect in a particular cellular process and, in response to this defect, activates a signal transduction pathway. Effectors activated by the signaling pathway initiate repair of the defect and halt cell cycle progression until the defect is corrected. If the defect cannot be repaired, the checkpoint pathway induces apoptosis. In what follows, we discuss the major checkpoint pathways that govern cell cycle progression.