Maf1 regulates intracellular lipid homeostasis in response to DNA damage response activation.

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 Caenorhabditis 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 target proteins, and expression of the Bcl-2 homology region genes, egl-1 and ced-13. Taken together, our results reveal mafr-1 as a component the DDR pathway response to regulating lipid homeostasis following exposure to UV genotoxic stress.