Xeroderma pigmentosum complementation group A and C (XPA and XPC) are critical proteins of the Nucleotide Excision Repair (NER) pathway, which resolves many of the UV radiation-induced DNA lesions such as cyclobutane pyrimidine dimers (CPDs) (51). XPA is recruited with other NER proteins and plays an important role in the assembly of repair proteins at the damage site. On the other hand, XPC facilitates the recognition of UV radiation-induced lesions specifically in transcriptionally inactive DNA, a process named global genome-NER (GG-NER) (51). As shown in Table 1 and Figure 4, a potential mechanism for the inhibition of NER by Wip1 is through dephosphorylation of XPA and XPC (52). XPA and XPC have p(S/T)Q motifs, which are consensus sequences for Wip1 that are targeted by PI3K-like kinases after DNA damage. Recombinant Wip1 protein efficiently dephosphorylated phosphopeptides corresponding to XPA S196 and XPC S892 (the PI3K-like kinase targets) in an in vitro phosphatase assay, and this was dependent on Wip1 phosphatase activity, since a phosphatase-dead mutant form of Wip1 (Wip1-D314A) was unable to dephosphorylate the phosphopeptides. The authors conclude that Wip1 may inhibit NER (see section 4.3.2.1 below) through dephosphorylation of XPA and XPC (52).
