p63 and p73, two p53 family members, play crucial roles in development and tumor 
suppression. p63 and p73 have multiple isoforms, which have similar or distinct 
biological functions. Transactivation (TA) isoforms of p63 and p73 have high 
similarity with p53 and often have biological functions similar to p53. p53 
plays an important role in nucleotide excision repair (NER) through 
transcriptional regulation of target genes involved in NER, including DDB2, XPC 
and GADD45. To investigate whether TAp63 and TAp73 play a similar role in NER, 
Saos2 cells with inducible expression of specific isoforms of TAp63 and TAp73, 
including TAp63α/β/γ and TAp73α/β/γ isoforms, were employed. Overexpression of 
TAp63γ significantly enhances NER of ultraviolet (UV)-induced DNA damage, 
including cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts, and 
enhances cell survival after UV irradiation in Soas2 cells. The enhancement of 
NER of UV-induced DNA damage by TAp63γ was also confirmed in H1299 cells with 
overexpression of TAp63γ. Consistently, knockdown of endogenous TAp63 decreases 
NER of UV-induced DNA damage in H1299 cells. TAp63α/β and TAp73α/β/γ isoforms do 
not have a clear effect on NER in Saos2 or H1299 cells. TAp63γ overexpression 
clearly induces the expression of DDB2, XPC and GADD45 at both RNA and protein 
levels. Furthermore, luciferase reporter assays show that TAp63γ 
transcriptionally activates DDB2, XPC and GADD45 genes through the regulation of 
the p53 binding elements in these genes. These results demonstrate that TAp63γ 
enhances NER to remove UV-induced DNA damage and maintain genomic stability 
through transcriptional induction of a set of NER proteins, which provides an 
additional important mechanism that contributes to the function of TAp63 in 
tumor suppression.