The novel tumor suppressor p33ING2 enhances nucleotide excision repair via inducement of histone H4 acetylation and chromatin relaxation.

p33ING2 is a novel candidate tumor suppressor, which has been shown to be involved in the regulation of gene transcription, cell cycle arrest, and apoptosis in a p53-dependent manner for maintaining the genomic stability. Previously, we showed that p33ING2 promoted UV-induced apoptosis in human melanoma cells. To further reveal the role of p33ING2 in cellular stress response to UV irradiation, we hypothesized that p33ING2 may enhance the repair of UV-damaged DNA, similarly to its homologue p33(ING1b). Using the host-cell reactivation assay, we show that overexpression of p33ING2 significantly enhances nucleotide excision repair of UV-induced DNA damage in melanoma cells in a p53-dependent manner. Furthermore, DNA repair is completely abolished in cells treated with p33ING2 small interfering RNA, suggesting that a physiologic level of p33ING2 is required for nucleotide excision repair. In addition, we found that p33ING2 is an essential factor for UV-induced rapid histone H4 acetylation, chromatin relaxation, and the recruitment of damage recognition protein, xeroderma pigmentosum group A protein, to the photolesions. These observations suggest that p33ING2 is required for the initial DNA damage sensing and chromatin remodeling in the nucleotide excision repair process.