Wang Jing, Chin Mei Yieng, Li Gang
Department of Medicine, Division of Dermatology, Jack Bell Research Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Cancer Res. 2006 Feb 15;66(4):1906-11. doi: 10.1158/0008-5472.CAN-05-3444.
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.
p33ING2是一种新型的候选肿瘤抑制因子，已被证明以p53依赖的方式参与基因转录调控、细胞周期阻滞和凋亡，以维持基因组稳定性。此前，我们发现p33ING2可促进人黑色素瘤细胞中紫外线诱导的凋亡。为了进一步揭示p33ING2在细胞对紫外线照射应激反应中的作用，我们推测p33ING2可能与其同源物p33(ING1b)类似，增强紫外线损伤DNA的修复。通过宿主细胞再激活试验，我们发现p33ING2的过表达以p53依赖的方式显著增强黑色素瘤细胞中紫外线诱导的DNA损伤的核苷酸切除修复。此外，用p33ING2小干扰RNA处理的细胞中DNA修复完全被消除，这表明核苷酸切除修复需要生理水平的p33ING2。此外，我们发现p33ING2是紫外线诱导的组蛋白H4快速乙酰化、染色质松弛以及损伤识别蛋白（着色性干皮病A组蛋白）募集到光损伤部位的关键因素。这些观察结果表明，p33ING2是核苷酸切除修复过程中初始DNA损伤感知和染色质重塑所必需的。
