Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Nuclear / genetics*
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Antigens, Nuclear / metabolism*
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Antimetabolites, Antineoplastic / pharmacology
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Azacitidine / pharmacology
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Blotting, Western
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Cell Culture Techniques
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DNA / drug effects
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DNA / genetics
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DNA / metabolism
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DNA Breaks, Double-Stranded / drug effects
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DNA Methylation* / drug effects
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DNA Methylation* / genetics
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DNA Repair* / drug effects
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DNA Repair* / genetics
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism*
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Gene Silencing / drug effects
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Hydrogen Peroxide / pharmacology
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Ku Autoantigen
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Mice
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Mice, Inbred BALB C
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Oxidants / pharmacology
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Promoter Regions, Genetic / drug effects
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Promoter Regions, Genetic / genetics
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Retinal Neurons / drug effects
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Retinal Neurons / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
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Up-Regulation / drug effects
Substances
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Antigens, Nuclear
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Antimetabolites, Antineoplastic
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DNA-Binding Proteins
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Oxidants
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DNA
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Hydrogen Peroxide
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Xrcc6 protein, mouse
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Ku Autoantigen
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Azacitidine