More recently, Lindqvist et al. showed that Wip1 is required for G2 checkpoint recovery competence (76). Cells were synchronized in G2, treated with Doxorubicin and then treated with ATM/ATR, Chk1/MAPKAP2, or p38 MAPK inhibitors to promote exit from G2 arrest. In this assay, cells with endogenous levels of Wip1 efficiently recovered from the G2 arrest, whereas cells with depleted Wip1 failed to do so (76). Furthermore, induction of Wip1 using a Tet-on system after DNA damage in the G2-arrested cells promoted checkpoint recovery. This was dependent on the phosphatase activity of Wip1, since expression of a phosphatase-dead mutant (D314A) failed to have this effect on G2 checkpoint recovery. The mechanism by which Wip1 maintains checkpoint recovery competence is through inhibition of p53, since failed G2 checkpoint recovery in Wip1 depleted cells was rescued by p53 depletion. Additionally, like HCT116 wild type cells, Wip1-depleted HCT116 p53−/− cells were able to recover from G2 arrest, indicating that activated p53 in Wip1-depleted cells caused the failure to recover from G2 arrest. Specifically, the authors showed that Wip1 inhibits the transcriptional repression of target
