| http://purl.uniprot.org/citations/25733871 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25733871 | http://www.w3.org/2000/01/rdf-schema#comment | "The DNA damage response (DDR) is crucial for genomic integrity. BRIT1 (breast cancer susceptibility gene C terminus-repeat inhibitor of human telomerase repeat transcriptase expression), a tumor suppressor and early DDR factor, is recruited to DNA double-strand breaks (DSBs) by phosphorylated H2A histone family, member X (γ-H2AX), where it promotes chromatin relaxation by recruiting the switch/sucrose nonfermentable (SWI-SNF) chromatin remodeler to facilitate DDR. However, regulation of BRIT1 recruitment is not fully understood. The baculovirus IAP repeat (BIR)-containing ubiquitin-conjugating enzyme (BRUCE) is an inhibitor of apoptosis protein (IAP). Here, we report a non-IAP function of BRUCE in the regulation of the BRIT1-SWI-SNF DSB-response pathway and genomic stability. We demonstrate that BRIT1 is K63 ubiquitinated in unstimulated cells and that deubiquitination of BRIT1 is a prerequisite for its recruitment to DSB sites by γ-H2AX. We show mechanistically that BRUCE acts as a scaffold, bridging the ubiquitin-specific peptidase 8 (USP8) and BRIT1 in a complex to coordinate USP8-catalyzed deubiquitination of BRIT1. Loss of BRUCE or USP8 impairs BRIT1 deubiquitination, BRIT1 binding with γ-H2AX, the formation of BRIT1 DNA damage foci, and chromatin relaxation. Moreover, BRUCE-depleted cells display reduced homologous recombination repair, and BRUCE-mutant mice exhibit repair defects and genomic instability. These findings identify BRUCE and USP8 as two hitherto uncharacterized critical DDR regulators and uncover a deubiquitination regulation of BRIT1 assembly at damaged chromatin for efficient DDR and genomic stability."xsd:string |
| http://purl.uniprot.org/citations/25733871 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1418335112"xsd:string |
| http://purl.uniprot.org/citations/25733871 | http://purl.uniprot.org/core/author | "Lu J."xsd:string |
| http://purl.uniprot.org/citations/25733871 | http://purl.uniprot.org/core/author | "Li K."xsd:string |
| http://purl.uniprot.org/citations/25733871 | http://purl.uniprot.org/core/author | "Ren J."xsd:string |
| http://purl.uniprot.org/citations/25733871 | http://purl.uniprot.org/core/author | "Ge C."xsd:string |
| http://purl.uniprot.org/citations/25733871 | http://purl.uniprot.org/core/author | "Che L."xsd:string |
| http://purl.uniprot.org/citations/25733871 | http://purl.uniprot.org/core/author | "Du C."xsd:string |
| http://purl.uniprot.org/citations/25733871 | http://purl.uniprot.org/core/author | "Pandita R.K."xsd:string |
| http://purl.uniprot.org/citations/25733871 | http://purl.uniprot.org/core/author | "Pandita T.K."xsd:string |
| http://purl.uniprot.org/citations/25733871 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/25733871 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/25733871 | http://purl.uniprot.org/core/pages | "E1210-9"xsd:string |
| http://purl.uniprot.org/citations/25733871 | http://purl.uniprot.org/core/title | "BRUCE regulates DNA double-strand break response by promoting USP8 deubiquitination of BRIT1."xsd:string |
| http://purl.uniprot.org/citations/25733871 | http://purl.uniprot.org/core/volume | "112"xsd:string |
| http://purl.uniprot.org/citations/25733871 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/25733871 |
| http://purl.uniprot.org/citations/25733871 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/25733871 |
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| http://purl.uniprot.org/uniprot/#_A0A8V8TR92-mappedCitation-25733871 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25733871 |