Résumé
Maintaining the genome integrity is crucial for cell survival and organism's homeostasis, necessitating vigilant surveillance of eventual DNA damage to promptly activate the DNA damage response (DDR). The DDR orchestrates cellular processes, notably cell cycle arrest and DNA repair, and is initiated by the kinases ATM/Tel1 and ATR/Mec1 (as known in humans/S. cerevisiae). Our team recently highlighted the significant role of lipids in modulating these kinases, notably ATM/Tel1. Specifically, the selective sequestration of sterols into lipid droplets (LD) stabilizes phosphatidylinositol-4-phosphate (PI4P) at the Golgi, to which ATM/Tel1 binds, thus titrating it from the nucleus, in turn facilitating completion of late DNA repair steps [1]. This raises the question of whether the DDR itself trigger sterol storage into LD, thus that there exist one or more effectors acting downstream of DDR regulating LD formation in response to DNA damage. Intriguingly, phosphoproteomic analyses in budding yeast point at a potential candidate: Opi1, a phosphatidic acid-regulated transcriptional repressor, is indeed phosphorylated in a DDR-dependent manner in response to DNA damage [2,3]. Using molecular and cellular biology approaches, microscopy and genetics, I will present a careful exploration of Opi1, especially on its phosphorylation, in mediating DDR-induced lipid droplet formation.