TY - JOUR
T1 - The roles of HMGB1-produced DNA gaps in DNA protection and aging biomarker reversal
AU - Yasom, Sakawdaurn
AU - Watcharanurak, Papitchaya
AU - Bhummaphan, Narumol
AU - Thongsroy, Jirapan
AU - Puttipanyalears, Charoenchai
AU - Settayanon, Sirapat
AU - Chalertpet, Kanwalat
AU - Khumsri, Wilunplus
AU - Kongkaew, Aphisek
AU - Patchsung, Maturada
AU - Siriwattanakankul, Chutha
AU - Pongpanich, Monnat
AU - Pin-on, Piyapat
AU - Jindatip, Depicha
AU - Wanotayan, Rujira
AU - Odton, Mingkwan
AU - Supasai, Suangsuda
AU - Oo, Thura Tun
AU - Arunsak, Busarin
AU - Pratchayasakul, Wasana
AU - Chattipakorn, Nipon
AU - Chattipakorn, Siriporn
AU - Mutirangura, Apiwat
N1 - Publisher Copyright:
© 2022 The Authors. FASEB BioAdvances published by the Federation of American Societies for Experimental Biology.
PY - 2022/6
Y1 - 2022/6
N2 - The endogenous DNA damage triggering an aging progression in the elderly is prevented in the youth, probably by naturally occurring DNA gaps. Decreased DNA gaps are found during chronological aging in yeast. So we named the gaps “Youth-DNA-GAPs.” The gaps are hidden by histone deacetylation to prevent DNA break response and were also reduced in cells lacking either the high-mobility group box (HMGB) or the NAD-dependent histone deacetylase, SIR2. A reduction in DNA gaps results in shearing DNA strands and decreasing cell viability. Here, we show the roles of DNA gaps in genomic stability and aging prevention in mammals. The number of Youth-DNA-GAPs were low in senescent cells, two aging rat models, and the elderly. Box A domain of HMGB1 acts as molecular scissors in producing DNA gaps. Increased gaps consolidated DNA durability, leading to DNA protection and improved aging features in senescent cells and two aging rat models similar to those of young organisms. Like the naturally occurring Youth-DNA-GAPs, Box A-produced DNA gaps avoided DNA double-strand break response by histone deacetylation and SIRT1, a Sir2 homolog. In conclusion, Youth-DNA-GAPs are a biomarker determining the DNA aging stage (young/old). Box A-produced DNA gaps ultimately reverse aging features. Therefore, DNA gap formation is a potential strategy to monitor and treat aging-associated diseases.
AB - The endogenous DNA damage triggering an aging progression in the elderly is prevented in the youth, probably by naturally occurring DNA gaps. Decreased DNA gaps are found during chronological aging in yeast. So we named the gaps “Youth-DNA-GAPs.” The gaps are hidden by histone deacetylation to prevent DNA break response and were also reduced in cells lacking either the high-mobility group box (HMGB) or the NAD-dependent histone deacetylase, SIR2. A reduction in DNA gaps results in shearing DNA strands and decreasing cell viability. Here, we show the roles of DNA gaps in genomic stability and aging prevention in mammals. The number of Youth-DNA-GAPs were low in senescent cells, two aging rat models, and the elderly. Box A domain of HMGB1 acts as molecular scissors in producing DNA gaps. Increased gaps consolidated DNA durability, leading to DNA protection and improved aging features in senescent cells and two aging rat models similar to those of young organisms. Like the naturally occurring Youth-DNA-GAPs, Box A-produced DNA gaps avoided DNA double-strand break response by histone deacetylation and SIRT1, a Sir2 homolog. In conclusion, Youth-DNA-GAPs are a biomarker determining the DNA aging stage (young/old). Box A-produced DNA gaps ultimately reverse aging features. Therefore, DNA gap formation is a potential strategy to monitor and treat aging-associated diseases.
KW - DNA damage
KW - DNA gap
KW - RIND-EDSB
KW - aging
KW - rejuvenation
KW - senescence
KW - youth-DNA-GAP
UR - http://www.scopus.com/inward/record.url?scp=85127256668&partnerID=8YFLogxK
U2 - 10.1096/fba.2021-00131
DO - 10.1096/fba.2021-00131
M3 - Article
AN - SCOPUS:85127256668
SN - 2573-9832
VL - 4
SP - 408
EP - 434
JO - FASEB BioAdvances
JF - FASEB BioAdvances
IS - 6
ER -