S-palmitoylation: An oily modification guardinggenome stability

S-palmitoylation is a dynamic post-translational lipid modification that regulates key cellular processes. It is mediated by aspartate-histidine-histidine-cysteine-family palmitoyltransferases (PATs) and reversed by acyl-protein thioesterases (APTs). This modification influences protein stability, function, subcellular trafficking, and membrane interactions. Emerging evidence identifies protein palmitoylation as a key regulator of genomic stability and integrity: it modulates DNA repair pathways, replication fork dynamics, and stress response mechanisms. Consequently, dysregulated palmitoylation cycles can lead to an impaired replication stress response, and chromosomal instability, which might drive oncogenesis. In this review, we examine the critical roles of S-palmitoylation in maintaining genome stability and speculate on its therapeutic potential in counteracting malignancy-associated genomic instability.