Academic Journal
Metalloprotease SPRTN/DVC1 Orchestrates Replication-Coupled DNA-Protein Crosslink Repair
العنوان: | Metalloprotease SPRTN/DVC1 Orchestrates Replication-Coupled DNA-Protein Crosslink Repair |
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المؤلفون: | Vaz, Bruno, Popović, Marta, Newman, Joseph A., Fielden, John, Aitkenhead, Hazel, Halder, Swagata, Singh, Abhay Narayan, Ramadan, Kristijan |
المصدر: | Molecular Cell |
بيانات النشر: | 12 month embargo |
سنة النشر: | 2016 |
المجموعة: | Ruđer Bošković Institute Zagreb: Full-text Institutional Repository (FULIR) |
مصطلحات موضوعية: | Biology, Biochemistry and Molecular Biology, Basic Medical Sciences |
الوصف: | The cytotoxicity of DNA-protein crosslinks (DPCs) is largely ascribed to their ability to block the progression of DNA replication. DPCs frequently occur in cells, either as a consequence of metabolism or exogenous agents, but the mechanism of DPC repair is not completely understood. Here, we characterize SPRTN as a specialized DNA- dependent and DNA replication-coupled metalloprotease for DPC repair. SPRTN cleaves various DNA binding substrates during S-phase progression and thus protects proliferative cells from DPC toxicity. Ruijs-Aalfs syndrome (RJALS) patient cells with monogenic and biallelic mutations in SPRTN are hypersensitive to DPC- inducing agents due to a defect in DNA replication fork progression and the inability to eliminate DPCs. We propose that SPRTN protease represents a specialized DNA replication-coupled DPC repair pathway essential for DNA replication progression and genome stability. Defective SPRTN-dependent clearance of DPCs is the molecular mechanism underlying RJALS, and DPCs are contributing to accelerated aging and cancer. |
نوع الوثيقة: | article in journal/newspaper |
وصف الملف: | application/pdf |
اللغة: | English |
Relation: | http://fulir.irb.hr/4207/; https://www.cell.com/molecular-cell/fulltext/S1097-2765(16)30584-6; http://fulir.irb.hr/4207/1/Vaz_Popovic_16_SPRTN_DPCR_MolCell%2Bsuppl.pdf |
DOI: | 10.1016/j.molcel.2016.09.032 |
الاتاحة: | http://fulir.irb.hr/4207/ http://fulir.irb.hr/4207/1/Vaz_Popovic_16_SPRTN_DPCR_MolCell%2Bsuppl.pdf https://www.cell.com/molecular-cell/fulltext/S1097-2765(16)30584-6 https://doi.org/10.1016/j.molcel.2016.09.032 |
Rights: | info:eu-repo/semantics/openAccess |
رقم الانضمام: | edsbas.D21F67D5 |
قاعدة البيانات: | BASE |
DOI: | 10.1016/j.molcel.2016.09.032 |
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