Chunk #39 — 4. WIP1 SUPPRESSES THE STRESS RESPONSE: UPDATE — 4.3. Wip1 and the UV response — 4.3.2. Wip1 dampens the UV response — 4.3.2.1. Inhibition of Nucleotide Excision Repair (NER)

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Regulation of the Wip1 phosphatase and its effects on the stress response.

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exhibited lower amounts of remaining CPDs after UV radiation compared to Wip1+/+ MEFs, whereas Wip1 overexpressing cells exhibited increased amounts of CPDs after UV radiation compared to the control cells. This effect was also shown in vivo by comparing CPD levels in the skin of UV irradiated Wip1−/− and Wip1+/+ mice. Wip1−/− MEFs and the skin from Wip1−/− mice showed a reduction in UV radiation-induced apoptosis, which was measured by the presence of cleaved Caspase-3 and PARP proteins as well as TUNEL staining (52). Thus, as shown in Figure 4, Wip1 negatively regulates NER after UV radiation (presumably through inactivation of XPA and XPC as discussed in section 4.1.1), and consequently enhances apoptosis through the higher levels of remaining CPDs.