Zhuang Jing, Ye Yiming, Liu Xuan, Li Fan, Pan Xueke, Chen Zhao, Luo Huihui, Ge Yihong, Ge Jian, Kaminski Joseph, Yu Keming
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, PR China.
Neuroreport. 2010 Mar 10;21(4):282-6. doi: 10.1097/WNR.0b013e328336ee7e.
Ku80 plays a critical role in DNA double strand breaks repair. However, Ku80 is silenced in mature neurocytes. In this study, the mechanism of Ku80 silencing and its role in DNA double strand break repair in retinal neurocytes was investigated. Our data show that Ku80 expression is activated in primary cultured retinal neurocytes after treatment with 5-azacytidine in vitro, whereas methylation of -179 bp in Ku80 promoter induces Ku80 silencing in retinal neurocytes. Ku80 reactivation in retinal neurocytes by 5-azacytidine enhances DNA integrity after treatment with H(2)O(2). Therefore, our data suggest Ku80 might be a target for reactivation to increase retinal neuronal DNA repair.
Ku80在DNA双链断裂修复中起关键作用。然而,Ku80在成熟神经细胞中沉默。在本研究中,研究了Ku80沉默的机制及其在视网膜神经细胞DNA双链断裂修复中的作用。我们的数据表明,体外经5-氮杂胞苷处理后,原代培养的视网膜神经细胞中Ku80表达被激活,而Ku80启动子中-179 bp处的甲基化诱导视网膜神经细胞中Ku80沉默。5-氮杂胞苷使视网膜神经细胞中的Ku80重新激活,在用H₂O₂处理后增强了DNA完整性。因此,我们的数据表明,Ku80可能是重新激活以增加视网膜神经元DNA修复的一个靶点。