Maf1 regulates intracellular lipid homeostasis in response to DDR activation

Abstract

Surveillance of DNA damage and maintenance of lipid metabolism are critical factors for general cellular homeostasis. We discovered that in response to DNA damage-inducing UV light exposure, intact C. elegans accumulate intracellular lipids in a dose dependent manner. The increase in intracellular lipids in response to exposure to UV light utilizes mafr-1, a negative regulator of RNA polymerase III and the apical kinases atm-1 and atl-1 of the DNA damage response (DDR) pathway. In the absence of exposure to UV light, the genetic ablation of mafr-1 results in the activation of the DDR including increased intracellular lipid accumulation, phosphorylation of ATM/ATR targets proteins, and expression of the Bcl-2 homology region genes, egl-1 and ced-13. Taken together, our study reveals a places mafr-1 as a component the DDR pathway response to regulating lipid homeostasis following exposure to UV genotoxic stress.