Research for SUMO-3-involved DNA synthesis induction after X-ray irradiation in human cells

痣基底细胞癌综合征（NBCCS），也称为Gorlin综合征或基底细胞痣综合征，是一种常染色体显性遗传病，易发生发育缺陷和癌症。来自（NBCCS）患者的成纤维细胞在x射线照射后显示DNA合成水平增加。我们发现辐照诱导DNA合成可能是通过下调SUMO-3基因在NBCCS细胞中的表达引起的。x射线照射8小时后，HeLa细胞DNA合成活性增加，SUMO-2/3表达下调。在这些条件下，转移抑制基因Nm23-H1的表达水平被改变。western blot分析证实x射线照射后NM23-H1蛋白减少。正如预期的那样，用NM23-H1的siRNA处理HeLa细胞导致DNA合成增强。这些结果表明，x射线照射后，SUMO- SUMO-2/3的表达与NM23-H1的稳定性密切相关，从而诱导了DNA的合成。x射线照射后，Nm23-H1可能被SUMO- SUMO-2/3修饰。Nm23-H1的减少似乎与sumoylation的减少偶然相关，而sumoylation又参与了x射线照射后DNA合成的诱导。

Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome or basal cell nevus syndrome, is an autosomal dominant disorder that predisposes to both developmental defects and cancer. Fibroblast cells derived from (NBCCS) patients show increased levels of DNA synthesis after X-ray irradiation. We found that the induction of DNA synthesis after irradiation could be caused by the down-regulation of SUMO-3 gene expression in NBCCS cells. Eight hours after X-ray irradiation, an increase in DNA synthesis activity was found in HeLa cells with knockdown of SUMO-2/3. Under these conditions, the expression levels of Nm23-H1, a metastatic suppressor gene, was altered. The decrease of NM23-H1 protein after X-ray irradiation was confirmed by western blot analysis. As expected, treatment of HeLa cells with the siRNA of NM23-H1 resulted in the enhancement of DNA synthesis. These findings suggest that the intimate relationship with the expression of SUMO- SUMO-2/3 and the stability of NM23-H1 after X-ray irradiation, lead to the induction of DNA synthesis.Nm23-H1 may be modified by SUMO- SUMO-2/3 after X-ray irradiation. The reduction of Nm23-H1 seems to be casually related to the decrease in sumoylation, which in turn, is involved in the induction of DNA synthesis after X-ray irradiation.