Journal
EPIGENOMICS
Volume 10, Issue 2, Pages 175-185Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/epi-2017-0096
Keywords
8-hydroxy-2 '-deoxyguanosine; aging; Alu interspersed repetitive element; Alu methylation; cancer; DNA damage; endogenous DNA damage; genomic instability; global DNA hypomethylation; RNA directed DNA methylation
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Funding
- Thailand Research Fund [DPG5980005, TRG5880214]
- Research Chair Grant from the National Science and Technology Development Agency (NSTDA), Thailand
- Anantara Siam Bangkok Hotel, Four Season Hotel Care for Cancer Fun Run
- Thai Red Cross Society
- Grants for Development of New Faculty Staff, Ratchadaphiseksomphot Endowment Fund, Chulalongkorn University [GDNS 59-009-23-005]
- Thailand Research Fund through the Royal Golden Jubilee Ph.D. Program [PHD/0131/2554]
- Chulalongkorn University
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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.
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