S-palmitoylation: An oily modification guardinggenome stability
Zheng X. Wu X. Wang L. Ouyang H. Damira Y. Peng B. Xu X.
September 2025Elsevier B.V.
DNA Repair
2025#153
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.
Cancer , DNA damage response , Genomic instability , Palmitoylation
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Shenzhen University General Hospital-Dehua Hospital Joint Research Center on Precision Medicine (sgh-dhhCPM), Dehua Hospital, Dehua, 362500, China
Key Laboratory of Soil Microbiology, Ministry of Agriculture, Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China
Guangdong Key Laboratory for Genome Stability & Disease Prevention and Carson International Cancer Center, Marshall Laboratory of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, 518060, China
Al-Farabi Kazakh National University, 71 Al-Farabi Avenue, Almaty, 050040, Kazakhstan
Shenzhen University General Hospital-Dehua Hospital Joint Research Center on Precision Medicine (sgh-dhhCPM)
Key Laboratory of Soil Microbiology
Guangdong Key Laboratory for Genome Stability & Disease Prevention and Carson International Cancer Center
Al-Farabi Kazakh National University
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