Integrated -omics approach reveals persistent DNA damage rewires lipid metabolism and histone hyperacetylation via MYS-1/Tip60.
Sci Adv
; 8(7): eabl6083, 2022 02 18.
Article
em En
| MEDLINE
| ID: mdl-35171671
ABSTRACT
Although DNA damage is intricately linked to metabolism, the metabolic alterations that occur in response to DNA damage are not well understood. We use a DNA repair-deficient model of ERCC1-XPF in Caenorhabditis elegans to gain insights on how genotoxic stress drives aging. Using multi-omic approach, we discover that nuclear DNA damage promotes mitochondrial ß-oxidation and drives a global loss of fat depots. This metabolic shift to ß-oxidation generates acetyl-coenzyme A to promote histone hyperacetylation and an associated change in expression of immune-effector and cytochrome genes. We identify the histone acetyltransferase MYS-1, as a critical regulator of this metabolic-epigenetic axis. We show that in response to DNA damage, polyunsaturated fatty acids, especially arachidonic acid (AA) and AA-related lipid mediators, are elevated and this is dependent on mys-1. Together, these findings reveal that DNA damage alters the metabolic-epigenetic axis to drive an immune-like response that can promote age-associated decline.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Histonas
/
Reparo do DNA
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Sci Adv
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos