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http://purl.uniprot.org/citations/26903517http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/26903517http://www.w3.org/2000/01/rdf-schema#comment"DNA double strand break (DSB) responses depend on the sequential actions of the E3 ubiquitin ligases RNF8 and RNF168 plus E2 ubiquitin-conjugating enzyme Ubc13 to specifically generate histone Lys-63-linked ubiquitin chains in DSB signaling. Here, we defined the activated RNF8-Ubc13∼ubiquitin complex by x-ray crystallography and its functional solution conformations by x-ray scattering, as tested by separation-of-function mutations imaged in cells by immunofluorescence. The collective results show that the RING E3 RNF8 targets E2 Ubc13 to DSB sites and plays a critical role in damage signaling by stimulating polyubiquitination through modulating conformations of ubiquitin covalently linked to the Ubc13 active site. Structure-guided separation-of-function mutations show that the RNF8 E2 stimulating activity is essential for DSB signaling in mammalian cells and is necessary for downstream recruitment of 53BP1 and BRCA1. Chromatin-targeted RNF168 rescues 53BP1 recruitment involved in non-homologous end joining but not BRCA1 recruitment for homologous recombination. These findings suggest an allosteric approach to targeting the ubiquitin-docking cleft at the E2-E3 interface for possible interventions in cancer and chronic inflammation, and moreover, they establish an independent RNF8 role in BRCA1 recruitment."xsd:string
http://purl.uniprot.org/citations/26903517http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m116.715698"xsd:string
http://purl.uniprot.org/citations/26903517http://purl.uniprot.org/core/author"Hura G.L."xsd:string
http://purl.uniprot.org/citations/26903517http://purl.uniprot.org/core/author"Tainer J.A."xsd:string
http://purl.uniprot.org/citations/26903517http://purl.uniprot.org/core/author"Edwards R.A."xsd:string
http://purl.uniprot.org/citations/26903517http://purl.uniprot.org/core/author"Glover J.N."xsd:string
http://purl.uniprot.org/citations/26903517http://purl.uniprot.org/core/author"Hendzel M.J."xsd:string
http://purl.uniprot.org/citations/26903517http://purl.uniprot.org/core/author"Ismail I.H."xsd:string
http://purl.uniprot.org/citations/26903517http://purl.uniprot.org/core/author"Hodge C.D."xsd:string
http://purl.uniprot.org/citations/26903517http://purl.uniprot.org/core/author"Xiao A.T."xsd:string
http://purl.uniprot.org/citations/26903517http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/26903517http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/26903517http://purl.uniprot.org/core/pages"9396-9410"xsd:string
http://purl.uniprot.org/citations/26903517http://purl.uniprot.org/core/title"RNF8 E3 Ubiquitin Ligase Stimulates Ubc13 E2 Conjugating Activity That Is Essential for DNA Double Strand Break Signaling and BRCA1 Tumor Suppressor Recruitment."xsd:string
http://purl.uniprot.org/citations/26903517http://purl.uniprot.org/core/volume"291"xsd:string
http://purl.uniprot.org/citations/26903517http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/26903517
http://purl.uniprot.org/citations/26903517http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/26903517
http://purl.uniprot.org/uniprot/#_A0A087WP26-mappedCitation-26903517http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26903517
http://purl.uniprot.org/uniprot/#_A0A087WPE1-mappedCitation-26903517http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26903517
http://purl.uniprot.org/uniprot/#_A0A087WPK5-mappedCitation-26903517http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26903517
http://purl.uniprot.org/uniprot/#_E0CY08-mappedCitation-26903517http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26903517
http://purl.uniprot.org/uniprot/#_A0A3Q4EC15-mappedCitation-26903517http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26903517
http://purl.uniprot.org/uniprot/#_A0A3Q4EGU3-mappedCitation-26903517http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26903517
http://purl.uniprot.org/uniprot/#_A0A1W2P7Z3-mappedCitation-26903517http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26903517