checkpoint

Meaning: Checkpoints are decision points that stop the cell cycle when something is wrong. Three are standard. The G1/S checkpoint (restriction point) checks cell size, nutrients, growth signals and DNA damage before replication. The G2/M checkpoint checks that DNA replication is complete and undamaged. The spindle assembly checkpoint, at metaphase to anaphase, checks that every chromosome is attached to spindle microtubules at its kinetochore. Progression is driven by cyclin-CDK complexes, and checkpoints work largely by inhibiting them. A stalled cell may repair the damage, enter G0, or undergo apoptosis.

On the MCAT: Passages describe a mutation, drug or knockout and ask where the cycle arrests or what happens to the cell. Know the pathway: DNA damage activates p53, which raises p21, which inhibits CDK and arrests the cell in G1. Rb, when hypophosphorylated, binds E2F and blocks S-phase gene expression; cyclin-CDK phosphorylation of Rb releases E2F. p53 and Rb are tumor suppressors, so loss of function lets cells with damaged DNA divide.

Common confusion: A checkpoint is a control step, not a phase of the cell cycle. Also, phosphorylated Rb is the inactive form, so the cell moves past the G1/S checkpoint when Rb is phosphorylated, not when it is active.