Mutations in SPRTN cause early onset hepatocellular carcinoma, genomic instability and progeroid features

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Topoisomerase 1 cleavage complexes and tumorigenesis

Germline mutations in SPRTN cause Ruijs–Aalfs syndrome (RJALS), a disorder characterized by genome instability, progeria and early onset hepatocellular carcinoma. Spartan, the protein encoded by SPRTN, is a nuclear metalloprotease that is involved in the repair of DNA–protein crosslinks (DPCs). Although Sprtn hypomorphic mice recapitulate key progeroid phenotypes of RJALS, whether this model ex...

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Spartan deficiency causes accumulation of Topoisomerase 1 cleavage complexes and tumorigenesis

Germline mutations in SPRTN cause Ruijs-Aalfs syndrome (RJALS), a disorder characterized by genome instability, progeria and early onset hepatocellular carcinoma. Spartan, the protein encoded by SPRTN, is a nuclear metalloprotease that is involved in the repair of DNA-protein crosslinks (DPCs). Although Sprtn hypomorphic mice recapitulate key progeroid phenotypes of RJALS, whether this model ex...

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SPRTN is a mammalian DNA-binding metalloprotease that resolves DNA-protein crosslinks

Ruijs-Aalfs syndrome is a segmental progeroid syndrome resulting from mutations in the SPRTN gene. Cells derived from patients with SPRTN mutations elicit genomic instability and people afflicted with this syndrome developed hepatocellular carcinoma. Here we describe the molecular mechanism by which SPRTN contributes to genome stability and normal cellular homeostasis. We show that SPRTN is a D...

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ژورنال

عنوان ژورنال: Nature Genetics

سال: 2014

ISSN: 1061-4036,1546-1718

DOI: 10.1038/ng.3103