Fig. 4

The mechanisms of RT-induced senescence and mitotic catastrophe in tumor cells. When p53 functions normally, ionizing radiation damages the DNA of tumor cells and activates the p53-p21 pathway and the p16INK4a-pRB pathway. The activation of p21 inhibits CDK1/2/4-cyclin complex, and the inhibition of CDK1-cyclin A complex arrests the cell cycle in the G2/M phase; p16INK4a inhibits CDK2-cyclin E/A complex and CDK4-cyclin D complex, promotes the dephosphorylation of pRB, and arrests the cell cycle in the G1/S phase, resulting in tumor cell senescence. When p53 is inactivated or mutated in tumor cells, ionizing radiation cannot activate the p53-p21 pathway, CDK1-cyclin A complex and CDK2-cyclin E/A complex are activated, and cells enter mitosis in advance; CDK2-cyclin E/A complex activation leads to centrosome hyperamplification. Tumor cells enter mitosis prematurely with unrepaired DNA damage, leading to mitotic catastrophe. CDK: cyclin-dependent kinase; pRB: retinoblastoma protein; RT: radiotherapy