{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hough SH"],"funding":["cambridgeuniversity | Cancer Research UK Cambridge Institute, University of Cambridge","Deutsche Forschungsgemeinschaft (DFG)","Cancer Research UK","Weizmann Institute of Science","Israeli Council for Higher Education","Weizmann Institute of Science (WIS)","Mark Foundation For Cancer Research (Mark Foundation)","Deutsche Forschungsgemeinschaft","European Research Council","Medical Research Council","cambridgeuniversity | Cancer Research UK Cambridge Institute, University of Cambridge (CRUK CI)","Mark Foundation For Cancer Research","Wellcome Trust","UKRI | Medical Research Council"],"pagination":["492-513"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12905269"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["18(2)"],"pubmed_abstract":["Ubiquitin E3 ligases play crucial roles in the DNA damage response (DDR) by modulating the turnover, localization, activation, and interactions of DDR and DNA replication proteins. We performed a CRISPR-Cas9 knockout screen focused on ubiquitin E3 ligases and related proteins with the DNA topoisomerase I inhibitor camptothecin. This led us to establish that MAEA, a core subunit of the CTLH E3 ligase complex, is a critical regulator of homologous recombination and the replication stress response. In tandem, we identified eight patients with variants in MAEA who present with a neurodevelopmental disorder that we term DIADEM (Developmental delay and Intellectual disability Associated with DEfects in MAEA). Analysis of patient-derived cell lines and mutation modeling reveal an underlying defec"],"journal":["EMBO molecular medicine"],"pubmed_title":["Loss of CTLH component MAEA impairs DNA repair and replication and leads to developmental delay."],"pmcid":["PMC12905269"],"funding_grant_id":["Outstanding Postdoctoral Women Fellowship","393547839-SFB 1361","ASPIRE II Award","KU 563/18-1","855741 (DDREAMM)","C6/A18796","855741","C17918/A28870","C17918/A2887","DRCPGM\\100005","SEBINT-2024/100003","Postdoctoral Career Development Award","WT203144","C17183/A23303","C9545/A29580","UKRI577","227014/Z/23/Z","206388/Z/17/Z"],"pubmed_authors":["Jhujh SS","Majumdar A","Damseh N","Awwad SW","Giannini R","Bartik L","Stewart GS","Mosler T","Belotserkovskaya R","McKee S","Carnie CJ","Smedley D","Bader A","Zagnoli Vieira G","Colin E","Galanty Y","Jackson SP","Hough SH","Cacheiro P","Beli P","Lewis OE","Thiffault I","Lam S","Smerdon SJ","Amudhavalli S","Thomas JC","Clement E","Fluss J"],"additional_accession":[]},"is_claimable":false,"name":"Loss of CTLH component MAEA impairs DNA repair and replication and leads to developmental delay.","description":"Ubiquitin E3 ligases play crucial roles in the DNA damage response (DDR) by modulating the turnover, localization, activation, and interactions of DDR and DNA replication proteins. We performed a CRISPR-Cas9 knockout screen focused on ubiquitin E3 ligases and related proteins with the DNA topoisomerase I inhibitor camptothecin. This led us to establish that MAEA, a core subunit of the CTLH E3 ligase complex, is a critical regulator of homologous recombination and the replication stress response. In tandem, we identified eight patients with variants in MAEA who present with a neurodevelopmental disorder that we term DIADEM (Developmental delay and Intellectual disability Associated with DEfects in MAEA). Analysis of patient-derived cell lines and mutation modeling reveal an underlying defec","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Feb","modification":"2026-07-15T21:23:13.894Z","creation":"2026-07-09T10:13:41.627Z"},"accession":"S-EPMC12905269","cross_references":{"pubmed":["41420108"],"doi":["10.1038/s44321-025-00352-x"]}}