SPRTN
Description
The SPRTN (SprT-like N-terminal domain) is a protein-coding gene located on chromosome 1.
Spartan (SPRTN) is a protein that in humans is encoded by the SPRTN gene. It is involved in DNA repair. Ruijs-Aalfs syndrome is an autosomal recessive genetic disorder. Characteristics of this disorder are features of premature aging, chromosome instability and development of hepatocellular carcinoma. Ruijs-Aalfs syndrome arises as a result of mutations in the SPRTN gene that encodes a metalloproteinase employed in the repair of protein-linked DNA breaks.
SPRTN is a DNA-dependent metalloendopeptidase that breaks down covalent DNA-protein cross-links (DPCs) during DNA synthesis. DPCs are highly toxic DNA lesions that block DNA replication and transcription. SPRTN helps maintain genomic integrity by removing DPCs. It works with the DNA replication machinery to specifically target and remove DPCs during DNA synthesis. SPRTN unfolds and breaks down the HMCES DNA-protein cross-link with the help of the BRIP1/FANCJ helicase. It also breaks down other DNA-binding proteins that are linked to DNA, such as TOP1, TOP2A, and histones H3 and H4. SPRTN can only break down DPCs that are not ubiquitinated. It is activated when the polymerase encounters a DPC and the helicase bypasses it. SPRTN helps bring VCP/p97 to sites of DNA damage. During normal DNA replication, SPRTN can activate CHEK1 by breaking it down, which removes CHEK1 from chromatin and activates it. However, SPRTN does not activate CHEK1 in response to DNA damage. SPRTN can also act as a "reader" of ubiquitinated PCNA, a protein that helps with DNA replication. SPRTN is recruited to sites of UV damage, where it interacts with ubiquitinated PCNA and RAD18. RAD18 is an E3 ubiquitin ligase that adds a single ubiquitin molecule to PCNA. SPRTN helps RAD18 attach to chromatin and is important for PCNA monoubiquitination. This creates a cycle where PCNA gets ubiquitinated more, which helps with translesion DNA synthesis, a process that allows DNA replication to continue even when there is damage. SPRTN forms a dimer with itself. It binds to PCNA (when it is ubiquitinated) through a PIP-box. It also binds to VCP/p97 through an SHP-box. SPRTN also interacts with RAD18, KCTD13, and POLD3.
SPRTN is also known as C1orf124, DVC1, PRO4323, spartan.
