{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Stingele J"],"funding":["Cancer Research UK","Francis Crick Institute","Robert A. Welch Chemistry Chair","Cancer Prevention and Research Institute of Texas","European Molecular Biology Organization","Department of Energy (DOE","European Research Council","EMBO","The Francis Crick Institute","Medical Research Council","National Cancer Institute","NCI NIH HHS","Wellcome Trust"],"pagination":["688-703"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5128726"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["64(4)"],"pubmed_abstract":["Covalent DNA-protein crosslinks (DPCs) are toxic DNA lesions that interfere with essential chromatin transactions, such as replication and transcription. Little was known about DPC-specific repair mechanisms until the recent identification of a DPC-processing protease in yeast. The existence of a DPC protease in higher eukaryotes is inferred from data in Xenopus laevis egg extracts, but its identity remains elusive. Here we identify the metalloprotease SPRTN as the DPC protease acting in metazoans. Loss of SPRTN results in failure to repair DPCs and hypersensitivity to DPC-inducing agents. SPRTN accomplishes DPC processing through a unique DNA-induced protease activity, which is controlled by several sophisticated regulatory mechanisms. Cellular, biochemical, and structural studies define "],"journal":["Molecular cell"],"pubmed_title":["Mechanism and Regulation of DNA-Protein Crosslink Repair by the DNA-Dependent Metalloprotease SPRTN."],"pmcid":["PMC5128726"],"funding_grant_id":["104558/Z/14/Z","ALTF 1656-2014","11581","ALTF 470-2015","FC0010048","PO1CA92584","10048","P01 CA092584","MC_U105178788"],"pubmed_authors":["Groll M","Maslen SL","Kjær S","Tsutakawa SE","Hewitt G","Boulton SJ","Sarek G","Alte F","Borg A","Bellelli R","Tainer JA","Stingele J","Skehel JM"],"additional_accession":[]},"is_claimable":false,"name":"Mechanism and Regulation of DNA-Protein Crosslink Repair by the DNA-Dependent Metalloprotease SPRTN.","description":"Covalent DNA-protein crosslinks (DPCs) are toxic DNA lesions that interfere with essential chromatin transactions, such as replication and transcription. Little was known about DPC-specific repair mechanisms until the recent identification of a DPC-processing protease in yeast. The existence of a DPC protease in higher eukaryotes is inferred from data in Xenopus laevis egg extracts, but its identity remains elusive. Here we identify the metalloprotease SPRTN as the DPC protease acting in metazoans. Loss of SPRTN results in failure to repair DPCs and hypersensitivity to DPC-inducing agents. SPRTN accomplishes DPC processing through a unique DNA-induced protease activity, which is controlled by several sophisticated regulatory mechanisms. Cellular, biochemical, and structural studies define ","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Nov","modification":"2026-04-07T17:57:05.655Z","creation":"2019-03-27T02:30:11Z"},"accession":"S-EPMC5128726","cross_references":{"pubmed":["27871365"],"doi":["10.1016/j.molcel.2016.09.031"]}}