{"doi":"10.17615/evfs-ha32","title":"A neomorphic cancer cell-specific role of MAGE-A4 in trans-lesion synthesis","abstract":"Trans-lesion synthesis (TLS) is an important DNA-damage tolerance mechanism that permits ongoing DNA synthesis in cells harbouring damaged genomes. The E3 ubiquitin ligase RAD18 activates TLS by promoting recruitment of Y-family DNA polymerases to sites of DNA-damage-induced replication fork stalling. Here we identify the cancer/testes antigen melanoma antigen-A4 (MAGE-A4) as a tumour cell-specific RAD18-binding partner and an activator of TLS. MAGE-A4 depletion from MAGE-A4-expressing cancer cells destabilizes RAD18. Conversely, ectopic expression of MAGE-A4 (in cell lines lacking endogenous MAGE-A4) promotes RAD18 stability. DNA-damage-induced mono-ubiquitination of the RAD18 substrate PCNA is attenuated by MAGE-A4 silencing. MAGE-A4-depleted cells fail to resume DNA synthesis normally following ultraviolet irradiation and accumulate γH2AX, thereby recapitulating major hallmarks of TLS deficiency. Taken together, these results demonstrate a mechanism by which reprogramming of ubiquitin signalling in cancer cells can influence DNA damage tolerance and probably contribute to an altered genomic landscape.","journal":"UNC Libraries","year":2020,"id":112946,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9618,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":534271,"name":"Alicia Greenwalt","orcid":null,"position":1,"is_corresponding":false},{"id":18212,"name":"Michael B. Major","orcid":"0000-0002-6753-8513","position":2,"is_corresponding":false},{"id":41818,"name":"Kenneth H. Pearce","orcid":"0000-0001-8138-5421","position":3,"is_corresponding":false},{"id":522500,"name":"Yang Yang","orcid":"0000-0001-7432-4735","position":4,"is_corresponding":false},{"id":18210,"name":"Feng Yan","orcid":"0000-0002-4855-5123","position":5,"is_corresponding":false},{"id":18208,"name":"Dennis Goldfarb","orcid":"0000-0002-1584-5423","position":6,"is_corresponding":false},{"id":534272,"name":"Yanzhe Gao","orcid":null,"position":7,"is_corresponding":false},{"id":533465,"name":"Satoshi Tateishi","orcid":"0000-0001-8307-4897","position":8,"is_corresponding":false},{"id":534273,"name":"Elizabeth Mutter‐Rottmayer","orcid":null,"position":9,"is_corresponding":false},{"id":487291,"name":"Cyrus Vaziri","orcid":"0000-0002-3081-8685","position":10,"is_corresponding":false},{"id":370072,"name":"Raquel C. Martinez‐Chacin","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:13:17.845093Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}