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http://purl.uniprot.org/citations/22589545http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22589545http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22589545http://www.w3.org/2000/01/rdf-schema#comment"The repair of DNA double strand breaks by homologous recombination relies on the unique topology of the chains formed by Lys-63 ubiquitylation of chromatin to recruit repair factors such as breast cancer 1 (BRCA1) to sites of DNA damage. The human RING finger (RNF) E3 ubiquitin ligases, RNF8 and RNF168, with the E2 ubiquitin-conjugating complex Ubc13/Mms2, perform the majority of Lys-63 ubiquitylation in homologous recombination. Here, we show that RNF8 dimerizes and binds to Ubc13/Mms2, thereby stimulating formation of Lys-63 ubiquitin chains, whereas the related RNF168 RING domain is a monomer and does not catalyze Lys-63 polyubiquitylation. The crystal structure of the RNF8/Ubc13/Mms2 ternary complex reveals the structural basis for the interaction between Ubc13 and the RNF8 RING and that an extended RNF8 coiled-coil is responsible for its dimerization. Mutations that disrupt the RNF8/Ubc13 binding surfaces, or that truncate the RNF8 coiled-coil, reduce RNF8-catalyzed ubiquitylation. These findings support the hypothesis that RNF8 is responsible for the initiation of Lys-63-linked ubiquitylation in the DNA damage response, which is subsequently amplified by RNF168."xsd:string
http://purl.uniprot.org/citations/22589545http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m112.359653"xsd:string
http://purl.uniprot.org/citations/22589545http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m112.359653"xsd:string
http://purl.uniprot.org/citations/22589545http://purl.uniprot.org/core/author"Neculai D."xsd:string
http://purl.uniprot.org/citations/22589545http://purl.uniprot.org/core/author"Neculai D."xsd:string
http://purl.uniprot.org/citations/22589545http://purl.uniprot.org/core/author"Dhe-Paganon S."xsd:string
http://purl.uniprot.org/citations/22589545http://purl.uniprot.org/core/author"Dhe-Paganon S."xsd:string
http://purl.uniprot.org/citations/22589545http://purl.uniprot.org/core/author"Edwards R.A."xsd:string
http://purl.uniprot.org/citations/22589545http://purl.uniprot.org/core/author"Edwards R.A."xsd:string
http://purl.uniprot.org/citations/22589545http://purl.uniprot.org/core/author"Glover J.N."xsd:string
http://purl.uniprot.org/citations/22589545http://purl.uniprot.org/core/author"Glover J.N."xsd:string
http://purl.uniprot.org/citations/22589545http://purl.uniprot.org/core/author"Leung C.C."xsd:string
http://purl.uniprot.org/citations/22589545http://purl.uniprot.org/core/author"Leung C.C."xsd:string
http://purl.uniprot.org/citations/22589545http://purl.uniprot.org/core/author"Campbell S.J."xsd:string
http://purl.uniprot.org/citations/22589545http://purl.uniprot.org/core/author"Campbell S.J."xsd:string
http://purl.uniprot.org/citations/22589545http://purl.uniprot.org/core/author"Hodge C.D."xsd:string
http://purl.uniprot.org/citations/22589545http://purl.uniprot.org/core/author"Hodge C.D."xsd:string
http://purl.uniprot.org/citations/22589545http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22589545http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22589545http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/22589545http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/22589545http://purl.uniprot.org/core/pages"23900-23910"xsd:string
http://purl.uniprot.org/citations/22589545http://purl.uniprot.org/core/pages"23900-23910"xsd:string