Like apoptosis, cell cycle arrest is critical in preventing DNA replication of a damaged genome. Functional studies have confirmed the role of Wip1 in the G1/S, intra-S, and G2/M checkpoints (Figure 4). Oiva-Trastoy et al. showed that cells overexpressing Wip1 have a dampened G2 arrest (as measured by flow cytometry) after IR (73). Additionally, flow cytometry analysis of Wip1−/− and wild type MEFs revealed that MEFs deficient in Wip1 have a significantly higher G2:M ratio (52.7) compared to the wild type (17.4), indicating that Wip1 plays a role in the transition from the G2 cell cycle phase to mitosis (74). Wip1 also functions in the G1 checkpoint, since synchronized Wip1−/− MEFs exhibited an exaggerated G1 arrest after IR compared to wild type due to higher p53 activity (74). These data indicate that Wip1 is likely to participate in the reversal of signaling important for the maintenance, and not initiation, of the G1 checkpoint (through p53 inhibition) since there was no difference at earlier time points following IR (74). Finally, evidence suggests that Wip1 has a function in the intra S-phase
