FIG. 8.

Model: p21 involvement in G₂/M checkpoint control? In nontransformed (p53⁺) cells, nuclear accumulation of p21 and binding to cyclin-Cdk complexes during G₁ and before mitosis (late G₂) may facilitate checkpoint implementation at the G₁/S-phase and G₂/M-phase transitions. In G₂, a p21-induced pause might potentiate the integration of G₂ checkpoint signals that regulate entry into mitosis through modulating the activity of cyclin A-Cdk2 and cyclin B1-Cdc2 complexes. Alternatively, increasing association of p21 with Cdk complexes at both transition points may sensitize these kinases to respond to further increases of p21 resulting from DNA damage. Whereas it seems that p53 activity (and p21 accumulation) is required for DNA damage-induced G₁ arrest, p53 (and p21) may be only a part of a redundant mechanism regulating G₂ arrest.