DNA-dependent protease; Regulator of UV-induced DNA damage response: acts as a 'reader' of ubiquitinated PCNA that enhances RAD18-mediated PCNA ubiquitination and translesion DNA synthesis (TLS). Recruited to sites of UV damage and interacts with ubiquitinated PCNA and RAD18, the E3 ubiquitin ligase that monoubiquitinates PCNA. Facilitates chromatin association of RAD18 and is required for efficient PCNA monoubiquitination, promoting a feed-forward loop to enhance PCNA ubiquitination and translesion DNA synthesis. Acts as a regulator of TLS by recruiting VCP/p97 to sites of DNA damage, possibly leading to extraction of DNA polymerase eta (POLH) by VCP/p97 to prevent excessive translesion DNA synthesis and limit the incidence of mutations induced by DNA damage. SPRTN is a DNA-dependent mammalian protease required for resolving cytotoxic DNA-protein crosslinks.
ohne Gefährdungspotential
SPRTN deficiency causes the premature aging and cancer predisposition disorder Ruijs-Aalfs syndrome.
Die ursächliche Beteiligung an der Entstehung von Tumoren ist nicht gezeigt.
Lopez-Mosqueda J et al., Elife. 2016 Nov 17;5. pii: e21491.
Stingele J et al., Mol Cell. 2016 Nov 17;64(4):688-703.
