Integrated -omics approach reveals persistent DNA damage rewires lipid metabolism and histone hyperacetylation via MYS-1/Tip60.

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 β-oxidation and drives a global loss of fat depots. This metabolic shift to β-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

SUBMITTER: Hamsanathan S 

PROVIDER: S-EPMC8849393 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature