Spartan deficiency causes accumulation of Topoisomerase 1 cleavage complexes and tumorigenesis
| العنوان: | Spartan deficiency causes accumulation of Topoisomerase 1 cleavage complexes and tumorigenesis |
|---|---|
| المؤلفون: | Hyun Ja Nam, Yusuke Kojima, Reeja S. Maskey, Thomas C. Smyrk, Annyoceli Santiago, Yuka Machida, Scott H. Kaufmann, Cynthia J. Sieben, Myoung Shin Kim, Yuichi J. Machida, Karen S. Flatten, Jan M. van Deursen, Darren J. Baker, Kevin L. Peterson |
| المصدر: | Nucleic Acids Research, 45, 8, pp. 4564-4576 Nucleic Acids Research, 45, 4564-4576 Nucleic Acids Research |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Genome instability, Carcinoma, Hepatocellular, Carcinogenesis, Chromosomal Proteins, Non-Histone, DNA damage, Gene Expression, Genome Integrity, Repair and Replication, Biology, medicine.disease_cause, DNA Adducts, Mice, 03 medical and health sciences, chemistry.chemical_compound, Progeria, Germline mutation, Genetics, medicine, Animals, Humans, Mice, Knockout, Topoisomerase, Liver Neoplasms, Syndrome, Aneuploidy, medicine.disease, Phenotype, Molecular biology, DNA-Binding Proteins, Disease Models, Animal, 030104 developmental biology, DNA Topoisomerases, Type I, Liver, chemistry, Proteolysis, Cancer research, biology.protein, Female, Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19], DNA |
| الوصف: | Contains fulltext : 174445.pdf (Publisher’s version ) (Open Access) 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 expressing low amounts of Spartan is prone to DPC repair defects and spontaneous tumors is unknown. Here, we showed that the livers of Sprtn hypomorphic mice accumulate DPCs containing Topoisomerase 1 covalently linked to DNA. Furthermore, these mice exhibited DNA damage, aneuploidy and spontaneous tumorigenesis in the liver. Collectively, these findings provide evidence that partial loss of Spartan impairs DPC repair and tumor suppression. |
| وصف الملف: | application/pdf |
| تدمد: | 0305-1048 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7c28aa5b4b0a228b7586252dcd78dd2e https://doi.org/10.1093/nar/gkx107 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....7c28aa5b4b0a228b7586252dcd78dd2e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 03051048 |
|---|