Figure 8. A model of the steps required for checkpoint adaptation after treatment with pharmacological concentrations of genotoxic agents.

Cells respond to cytotoxic pharmacological amounts of genotoxic agents through a series of key biochemical events that include: increase in γH2AX levels and increase in phospho-Ser³⁴⁵ Chk1 levels before adaptation. Cells that have undergone checkpoint adaptation still have γH2AX, but a greatly reduced level of phospho-Ser³⁴⁵ Chk1, high Cdk1 activity and phospho-Ser¹⁰ histone H3. Although the majority of cells will die, a small number of cells survive, giving rise to cells that have major changes in their genome.