ScienceAsia 51S (2023): 1-8 |doi:
10.2306/scienceasia1513-1874.2023.s005
DNA protection epigenetic marks: "Youth-associated genomic
stabilization DNA gaps" (youth-DNA-gaps)
Papitchaya Watcharanuraka, Apiwat Mutirangurab,*,?
ABSTRACT: Global hypomethylation promotes genomic instability by increasing DNA damage. The accumulation of
DNA damage contributes to cellular senescence, which is implicated in the aging process and various age-associated
diseases, including age-associated non-communicable diseases (NCDs). Methylated youth-DNA-gap epigenetic mark
produced by the molecular scissoring activity of Box A of HMGB1 molecule or rejuvenating DNA by genomic stability
molecule to strengthen DNA (REDGEM-S-DNA) protects DNA from damage by relieving the double helix torsion
stress during replication or transcription. The activation through active or passive release of intranuclear HMGB1
causes youth-DNA-gaps depletion. The reduction of youth-DNA-gaps results in DNA damage accumulation and global
hypomethylation. Restoring the function of the youth-DNA-gap epigenetic mark through treatment of Box A of HMGB1
leads to reduced cellular senescence, rejuvenation of aging cells, and improved organ function. Therefore, HMGB1-Box
A or REDGEM-S-DNA gene therapy to produce DNA gaps could be a promising strategy for treating aging conditions
and age-related diseases.
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| a |
Faculty of Medical Technology, Prince of Songkla University, Songkhla 90110 Thailand |
| b |
Center of Excellence in Molecular Genetics of Cancer and Human Disease, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok 10330 Thailand |
* Corresponding author, E-mail: apiwat.mutirangura@gmail.com
Received 16 Oct 2024, Accepted 1 Mar 2025
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