Open AccessMaf1 regulates intracellular lipid homeostasis in response to DDR activation
Author(s) -
Amy M. Hammerquist,
Wilber Escorcia,
Sean P. Curran
Publication year - 2021
Publication title -
molecular biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.463
H-Index - 225
eISSN - 1939-4586
pISSN - 1059-1524
DOI - 10.1091/mbc.e20-06-0378
Subject(s) - biology , intracellular , dna damage , microbiology and biotechnology , phosphorylation , kinase , homeostasis , lipid metabolism , signal transduction , dna repair , genetic screen , dna , biochemistry , gene , phenotype
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.