Résumé
We have asked if nLD display any connection with genome stability. For this, we evaluated whether multiple genotoxins, each harming DNA differently, alter the frequency of nLD present in cells. We now report that nLD formation is stimulated, in a conserved manner, in response to replicative stress [1]. On a functional note, we found that the increase in phospholipids in the nucleoplasmic space, as that generated when nLD enter the nucleus, exacerbates the intensity of the DDR and, of relevance, this stricter DDR translates into increased genome integrity [2]. This is particularly hot when considering that ATR, the orchestrator of the response to replicative stress, has been found in three previous studies to sense the physico-chemical properties of the nuclear envelope phospholipids. We now aspire to explore this fully new research avenue. To this end, we hereby postulate that nLD act as functional platforms for DNA damage signaling, stabilization and / or repair. With these non-exclusive hypotheses in mind, we are currently dissecting the chromatin patterns surrounding nLD by electron microscopy, for nLD have been proposed to modulate these. We have developed a variant of the comet assay, COLD (comet-on-lipid-droplets), allowing us to assess the chromatin-stabilizing potential of nLD. We interfere with nLD birth and assess the impact on genome stability and on replication fork progression. Further, we aim at addressing the nLD-associated proteome and lipidome during replicative stress to better understand their role. In sum, we want to create awareness of the existence, the importance, and the manipulation opportunities of nLD in genome stability. Given that both replicative stress and lipids are of paramount importance in cancer initiation, progression, and relapse, understanding this poorly explored link is of utmost importance.