DNA Damage Promotes ER Stress Resistance Through Elevation Of Unsaturated Phosphatidylcholine In C. Elegans

DNA damage triggers the cellular adaptive response to arrest proliferation and repair DNA damage;when damage is too severe to be repaired,apoptosis is initiated to prevent the spread of genomic insults.However,how cells endure DNA damage to maintain cell function remains largely unexplored.By using C.elegans as a model,we report that DNA damage elicits cell maintenance programs including the endoplasmic reticulum(ER)unfolded protein response(UPR^ER).Mechanistically,sublethal DNA damage unexpectedly suppresses apoptotic genes in C.elegans,which in turn increases the activity of the IRE-1/XBP-1 branch of the UPR^ER by elevating unsaturated phosphatidylcholine(PC).In addition,UPRER activation requires silencing of the lipid regulator SKN-1.DNA damage suppresses SKN-1activity to increase unsaturated PC and activate UPR^ER.These findings reveal the UPR^ER activation as an organismal adaptive response that is important to maintain cell function during DNA damage.