assays showed that Wip1 dephosphorylated gamma-H2AX phosphopetides, and co-immunoprecipitation assays showed that Wip1 physically interacts with H2AX. Furthermore, deletion of Wip1 enhanced gamma-H2AX levels after genotoxic stress, whereas overexpression of Wip1 reduced gamma-H2AX levels, which was ATM-independent (7, 8, 56). Importantly, our group showed that formation of gamma-H2AX foci, per se, was not affected by Wip1 overexpression, since gamma-H2AX foci were observed in cells overexpressing Wip1 shortly after IR exposure (10 minutes) at levels comparable to those in control cells (7). Together, these studies showed that Wip1 is a gamma-H2AX phosphatase and is important for removal of gamma-H2AX after genotoxic stress (Table 1 and Figure 4).
