The DNA Damage Response kinase ATM restricts Golgi extension

Abstract The master kinases of the DNA damage response (DDR), ATR, ATM and DNA-PK, become active in response to DNA damage and orchestrate a downstream wave of phosphorylations contributing to DNA damage repair and preservation of cellular homeostasis. Of them, we recently demonstrated that ATM binds the pool of the lipid phosphatidyl-inositol-4-phosphate (PI4P) situated at the Golgi membrane. Depending on PI4P availability at Golgi membranes, ATM is more or less titrated away from the nucleus, which translates into responses to nuclear DNA damage of matching intensity. Building on this knowledge, in this work we asked if, beyond the Golgi merely serving as a docking platform that retains ATM away from the nucleus, ATM does exert any role important for Golgi biology. We found that ATM maintains Golgi morphology by counteracting its excessive deployment. This occurs both by its mere presence (likely antagonizing the Golgi-stretching action of the protein GOLPH3) and by phosphorylating Golgi-resident substrates. Of relevance, we also report that the morphological alterations caused to the Golgi without ATM affect the biology of a model Golgi cargo. Our findings nourish the growing evidence that kinases of ATM’s family display functional interactions with membranes and highlights an underappreciated crosstalk between the Golgi and the nucleus. Competing Interest Statement The authors have declared no competing interest. Abbreviations - ATM - ataxia telangiectasia-mutated kinase - ATR - ataxia telangiectasia and Rad3-related kinase - DDR - DNA damage response - DNA-PK - DNA-dependent protein kinase - MMS - methyl methane sulfonate - MTOC - microtubule organizing center - PIKK - phosphatidyl- inositol-3-kinase-related kinase - PI4P - phosphatidyl-inositol-4-phosphate - SEM - standard error of the mean