DNA-dependent metalloprotease SPRTN (SPRTN)

SPRTN is a specialized, DNA-dependent metalloprotease critical for maintaining genome integrity by cleaving DNA-protein crosslinks (DPCs) that would otherwise hinder DNA replication[1][2]. SPRTN activity is tightly regulated: it is recruited to stalled replication forks via PCNA-interacting and ubiquitin-binding domains, is activated by specific DNA structures, and is controlled by posttranslational modifications such as ubiquitination to prevent inappropriate proteolysis[1][2][4]. Its proteolytic activity is restricted to DNA-bound substrates during S phase, thereby resolving cytotoxic lesions and preventing replication stress[1]. Dysfunction or mutations in SPRTN are implicated in Ruijs–Aalfs syndrome, a progeroid disorder characterized by genomic instability, premature aging, and a predisposition to cancers, especially hepatocellular carcinoma[1][3][5]. SPRTN also coordinates DNA damage tolerance pathways, influencing the switch between replicative and translesion synthesis DNA polymerases and broader aspects of DNA repair and genome maintenance[1][2].

Other names

DVC1SpartanC1orf124PRO4323DNA damage protein targeting VCPDNA damage-targeting VCP (p97) adaptorzinc finger RAD18 domain-containing proteinSprT-like N-terminal domain