Fig 7.

Proposed model of how Chk1 regulates oxidative DNA damage in HCT116 colorectal cancer cells. (A) H₂O₂-induced DNA damage activates Chk1 in wt cells, which prevents progression into mitosis via G₂ arrest. Cells with non-repairable DNA damage go into apoptosis, whereas cells with repairable DNA damage slip through mitosis and arrest in G₁ associated with senescence. (B) H₂O₂-induced DNA damage activates Chk1 in p53^–/–/ p21^–/– cells, preventing progression into mitosis via late G₂ arrest. Because of a lack or low levels of p53/p21^WAF1, respectively, cells undergo premature mitosis with their DNA largely unrepaired, which drives these cells into mitotic catastrophe. Importantly, Chk1 is required for recovery from G₂ checkpoint arrest, leading to long-term senescence (A) and mitotic catastrophe (B).