DNA demethylation in retinal neurocytes contributes to the upregulation of DNA repair protein, Ku80.
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.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, PR China.
Jing
J
Zhuang
Yiming
Y
Ye
Xuan
X
Liu
Fan
F
Li
Xueke
X
Pan
Zhao
Z
Chen
Huihui
H
Luo
Yihong
Y
Ge
Jian
J
Ge
Joseph
J
Kaminski
Keming
K
Yu
D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics* / Q000378:metabolism*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000494:pharmacology; D015153:Blotting, Western; D018929:Cell Culture Techniques; D004247:DNA / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D020868:Gene Silencing / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D000072200:Ku Autoantigen; D051379:Mice; D008807:Mice, Inbred BALB C; D016877:Oxidants / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D055351:Retinal Neurons / Q000187:drug effects / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects
D034961:Antigens, Nuclear; D000964:Antimetabolites, Antineoplastic; D004268:DNA-Binding Proteins; D016877:Oxidants; D004247:DNA; D006861:Hydrogen Peroxide; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen; D001374:Azacitidine