Metalloprotease SPRTN-DVC1 Orchestrates Replication-Coupled DNA-Protein Crosslink RepairReportar como inadecuado




Metalloprotease SPRTN-DVC1 Orchestrates Replication-Coupled DNA-Protein Crosslink Repair - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Reference: Vaz, B, Popovic, M, Newman, JA et al., (2016). Metalloprotease SPRTN/DVC1 Orchestrates Replication-Coupled DNA-Protein Crosslink Repair. Molecular Cell.Citable link to this page:

 

Metalloprotease SPRTN/DVC1 Orchestrates Replication-Coupled DNA-Protein Crosslink Repair

Abstract: 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.

Publication status:PublishedPeer Review status:Peer reviewedVersion:Publisher's versionDate of acceptance:2016-09-22 Funder: Medical Research Council   Funder: John Fell Fund   Funder: University of Oxford   Funder: Wellcome Trust   Funder: Kennedy Trust Fund   Funder: National Health and Medical Research Council of Australia   Notes:© 2016 Elsevier Inc. Available under a Creative Commons license. Open Access funded by Medical Research Council.

Bibliographic Details

Publisher: Elsevier

Publisher Website: http://www.elsevier.com

Journal: Molecular Cellsee more from them

Publication Website: http://www.journals.elsevier.com/neuroimage/

Issue Date: 2016-10-27Identifiers

Doi: https://doi.org/10.1016/j.molcel.2016.09.032

Issn: 1097-2765

Eissn: 1097-4164

Uuid: uuid:e0cb7a74-a2a2-4e0d-8f36-586474243c0c

Urn: uri:e0cb7a74-a2a2-4e0d-8f36-586474243c0c

Pubs-id: pubs:655588 Item Description

Type: journal-article;

Version: Publisher's versionKeywords: Article

Relationships





Autor: Vaz, B - Oxford, MSD, Oncology, CRUK-MRC Ox Inst for Radiation Oncology - - - Popovic, M - Oxford, MSD, Oncology, CRUK-MRC Ox Ins

Fuente: https://ora.ox.ac.uk/objects/uuid:e0cb7a74-a2a2-4e0d-8f36-586474243c0c



DESCARGAR PDF




Documentos relacionados