Nguyen et al. were the first to show inhibition of NER by Wip1 (Figure 4) (52). Wip1−/− MEFs had almost a three-fold increase in NER activity as measured by the ability of the cells to repair a UV-irradiated luciferase reporter plasmid. Likewise, overexpression of wild type Wip1 (but not a nonfunctional mutant Wip1) inhibited NER by over 30%, and this was p53-independent, since overexpression of Wip1 in a p53−/− cell line, Saos2, similarly reduced NER activity by over 40%. As expected, Wip1 overexpression had no effect on the low level of reporter activity exhibited by cells deficient in xeroderma pigmentosum complementation group D (XPD), but did significantly reduce reporter activity in XPD cells complemented with an XPD expression vector. Similar effects of Wip1 on NER activity were also shown by measuring the levels of unrepaired CPDs (51, 52). Wip1−/− MEFs 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
