Chunk #40 — 4. WIP1 SUPPRESSES THE STRESS RESPONSE: UPDATE — 4.3. Wip1 and the UV response — 4.3.2. Wip1 dampens the UV response — 4.3.2.2. Dampening of the DDR
Although not directly produced by UV radiation exposure, DSBs can be formed indirectly through, for example, the stalling of replication forks. This is evident by the measurement of DSBs by comet assays and the presence of phosphorylated DDR proteins such as gamma-H2AX, ATM, and NBS1 after UV radiation exposure (51, 59), which Oh et al. showed was independent of an intact NER system, as this occurred in cells deficient in the NER helicase, XPB (59). Since Wip1 is induced after UV radiation exposure in normal human fibroblasts, it most likely plays a role in dephosphorylating and inactivating the DDR proteins after UV radiation. As described in section 4.3.1.2, Wip1 was not induced by UV radiation exposure in XPB fibroblasts (59). Additionally, immunofluorescence assays revealed that foci corresponding to phosphorylated and activated DDR proteins such as gamma-H2AX and phospho-ATM were resolved 24 hours after UV radiation exposure when Wip1 expression was high. However, these foci persisted in the XPB cells. Since Wip1 was not induced in XPB cells and since DDR proteins such as gamma-H2AX and phospho-ATM are Wip1 targets, the
