Figure 4.

G2-checkpoint - no passage for cells with damaged DNA. During the G2-phase cells prepare for genomic and cytoplasmic separation. An ATR-/ATM-driven DNA damage response (originating from DNA lesions which are shown at the top) leads to inhibition of Cdk1 (shown in the lower part) and hence arrests cells with signs of DNA damage at the G2-phase until the problem is solved. Therapeutic agents such as etoposide or anthracyclins (shown in yellow) work by induction of a cell cycle arrest in the G2-phase. Leukemia-promoting alterations, such as overexpression of Plk1, FOXM1, SET or loss of function of p53 (marked in red) allow cells to override the DNA damage response and allow the accumulation of oncogenic mutations. Different therapeutic approaches aim at reconstituting the DNA damage response by stabilization of p53. See text for details.