Maturada Patchsung1, Sirapat Settayanon2, Monnat Pongpanich3,4, Dharm Mutirangura4, Pornrutsami Jintarith5, Apiwat Mutirangura4,6. 1. Inter-Department Program of Biomedical Sciences, Faculty of Graduate School, Chulalongkorn University, Bangkok, Thailand. 2. Program of Medical Science, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 3. Department of Mathematics & Computer Science, Faculty of Science, Chulalongkorn University, Bangkok, Thailand. 4. Center for Excellence in Molecular Genetics of Cancer & Human Diseases, Chulalongkorn University, Bangkok, Thailand. 5. Omics Sciences & Bioinformatics Center, Faculty of Science, Chulalongkorn University, Bangkok, Thailand. 6. Department of Tropical Nutrition & Food Science, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Abstract
Global DNA hypomethylation promoting genomic instability leads to cancer and deterioration of human health with age. AIM: To invent a biotechnology that can reprogram this process. METHODS: We used Alu siRNA to direct Alu interspersed repetitive sequences methylation in human cells. We evaluated the correlation between DNA damage and Alu methylation levels. RESULTS: We observed an inverse correlation between Alu element methylation and endogenous DNA damage in white blood cells. Cells transfected with Alu siRNA exhibited high Alu methylation levels, increased proliferation, reduced endogenous DNA damage and improved resistance to DNA damaging agents. CONCLUSION: Alu methylation stabilizes the genome by preventing accumulation of DNA damage. Alu siRNA could be useful for evaluating reprograming of the global hypomethylation phenotype in cancer and aging cells.
Global DNA hypomethylation promoting genomic instability leads to cancer and deterioration of human health with age. AIM: To invent a biotechnology that can reprogram this process. METHODS: We used Alu siRNA to direct Alu interspersed repetitive sequences methylation in human cells. We evaluated the correlation between DNA damage and Alu methylation levels. RESULTS: We observed an inverse correlation between Alu element methylation and endogenous DNA damage in white blood cells. Cells transfected with Alu siRNA exhibited high Alu methylation levels, increased proliferation, reduced endogenous DNA damage and improved resistance to DNA damaging agents. CONCLUSION:Alu methylation stabilizes the genome by preventing accumulation of DNA damage. Alu siRNA could be useful for evaluating reprograming of the global hypomethylation phenotype in cancer and aging cells.
Entities:
Keywords:
8-hydroxy-2′-deoxyguanosine; Alu interspersed repetitive element; Alu methylation; DNA damage; RNA directed DNA methylation; aging; cancer; endogenous DNA damage; genomic instability; global DNA hypomethylation
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