{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Schmidt CK"],"funding":["Cancer Research UK","European Research Council","Wellcome Trust"],"pagination":["1458-1470"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4894550"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["17(11)"],"pubmed_abstract":["Ubiquitylation is crucial for proper cellular responses to DNA double-strand breaks (DSBs). If unrepaired, these highly cytotoxic lesions cause genome instability, tumorigenesis, neurodegeneration or premature ageing. Here, we conduct a comprehensive, multilayered screen to systematically profile all human ubiquitin E2 enzymes for impacts on cellular DSB responses. With a widely applicable approach, we use an exemplary E2 family, UBE2Ds, to identify ubiquitylation-cascade components downstream of E2s. Thus, we uncover the nuclear E3 ligase RNF138 as a key homologous recombination (HR)-promoting factor that functions with UBE2Ds in cells. Mechanistically, UBE2Ds and RNF138 accumulate at DNA-damage sites and act at early resection stages by promoting CtIP ubiquitylation and accrual. This wor"],"journal":["Nature cell biology"],"pubmed_title":["Systematic E2 screening reveals a UBE2D-RNF138-CtIP axis promoting DNA repair."],"pmcid":["PMC4894550"],"funding_grant_id":["18796","268536","WT092096","C6946/A14492","092096","A11224","11224","C6/A11224"],"pubmed_authors":["Demir M","Beli P","Galanty Y","Cornwell M","Jackson SP","Sczaniecka-Clift M","Coates J","Schmidt CK","Jhujh S"],"additional_accession":[]},"is_claimable":false,"name":"Systematic E2 screening reveals a UBE2D-RNF138-CtIP axis promoting DNA repair.","description":"Ubiquitylation is crucial for proper cellular responses to DNA double-strand breaks (DSBs). If unrepaired, these highly cytotoxic lesions cause genome instability, tumorigenesis, neurodegeneration or premature ageing. Here, we conduct a comprehensive, multilayered screen to systematically profile all human ubiquitin E2 enzymes for impacts on cellular DSB responses. With a widely applicable approach, we use an exemplary E2 family, UBE2Ds, to identify ubiquitylation-cascade components downstream of E2s. Thus, we uncover the nuclear E3 ligase RNF138 as a key homologous recombination (HR)-promoting factor that functions with UBE2Ds in cells. Mechanistically, UBE2Ds and RNF138 accumulate at DNA-damage sites and act at early resection stages by promoting CtIP ubiquitylation and accrual. This wor","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015 Nov","modification":"2025-04-19T15:01:38.255Z","creation":"2019-03-27T02:15:23Z"},"accession":"S-EPMC4894550","cross_references":{"pubmed":["26502057"],"doi":["10.1038/ncb3260"]}}