DNA-dependent metalloprotease SPRTN (SPRTN) (SPRTN)

DNA-dependent metalloprotease SPRTN (SPRTN), also known as Spartan, is an essential enzyme responsible for the repair of DNA-protein crosslinks (DPCs), which are toxic lesions that impede DNA replication and transcription (UniProt Q9H040). SPRTN functions by proteolytically cleaving proteins that have become covalently trapped on DNA, such as Topoisomerase 1 or proteins crosslinked by endogenous aldehydes, thereby allowing the replication fork to progress (Vaz et al., 2016, Molecular Cell). This activity is tightly regulated and coupled to DNA replication to prevent unscheduled degradation of chromatin proteins (Moro et al., 2023, Nature Communications). Mutations in the SPRTN gene are the underlying cause of Ruijs-Aalfs syndrome (RJALS), a rare autosomal recessive disorder characterized by genomic instability, early-onset hepatocellular carcinoma, and progeroid features (Lessel et al., 2014, Nature Genetics). While no clinical drugs currently target SPRTN, it is an emerging target in oncology research; its inhibition is hypothesized to sensitize cancer cells to chemotherapeutic agents that induce DPCs (Reinking et al., 2020, Journal of Biological Chemistry). However, because SPRTN is vital for maintaining genome integrity, therapeutic strategies must carefully manage the risk of inducing systemic DNA damage and premature aging (Stingele et al., 2016, Molecular Cell).

Other names

SpartanDVC1C1orf124Sprat-like proteinDNA-binding protein SPRTN

Proteolytic degradation of DNA-protein crosslinks to facilitate DNA replication fork progression; theoretical inhibition to sensitize cancer cells to DNA-damaging agents.