{"doi":"10.1073/pnas.2115999119","title":"LINE-1 expression in cancer correlates with p53 mutation, copy number alteration, and S phase checkpoint","abstract":"Retrotransposons are genomic DNA sequences that copy themselves to new genomic locations via RNA intermediates; LINE-1 is the only active and autonomous retrotransposon in the human genome. The mobility of LINE-1 is largely repressed in somatic tissues but is derepressed in many cancers, where LINE-1 retrotransposition is correlated with p53 mutation and copy number alteration (CNA). In cell lines, inducing LINE-1 expression can cause double-strand breaks (DSBs) and replication stress. Reanalyzing multiomic data from breast, ovarian, endometrial, and colon cancers, we confirmed correlations between LINE-1 expression, p53 mutation status, and CNA. We observed a consistent correlation between LINE-1 expression and the abundance of DNA replication complex components, indicating that LINE-1 may also induce replication stress in human tumors. In endometrial cancer, high-quality phosphoproteomic data allowed us to identify the DSB-induced ATM-MRN-SMC S phase checkpoint pathway as the primary DNA damage response (DDR) pathway associated with LINE-1 expression. Induction of LINE-1 expression in an in vitro model led to increased phosphorylation of MRN complex member RAD50, suggesting that LINE-1 directly activates this pathway.","journal":"Proceedings of the National Academy of Sciences","year":2022,"id":233895,"datarank":0.7091081728068512,"base_score":4.727387818712341,"endowment":4.727387818712341,"self_citation_contribution":0.7091081728068512,"citation_network_contribution":0.0,"self_endowment_contribution":0.7091081728068512,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":112,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9507,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":2213,"name":"Xuya Wang","orcid":"0000-0001-5538-5217","position":1,"is_corresponding":false},{"id":392739,"name":"Carlos Mendez‐Dorantes","orcid":"0000-0002-8190-8568","position":2,"is_corresponding":false},{"id":238056,"name":"Paolo Mita","orcid":"0000-0002-2093-4906","position":3,"is_corresponding":false},{"id":31714,"name":"Song Cao","orcid":"0000-0003-2965-5855","position":4,"is_corresponding":false},{"id":567323,"name":"Mark Grivainis","orcid":"0000-0001-8156-7153","position":5,"is_corresponding":false},{"id":108228,"name":"Li Ding","orcid":"0000-0003-1517-2975","position":6,"is_corresponding":false},{"id":463098,"name":"John LaCava","orcid":"0000-0002-6307-7713","position":7,"is_corresponding":false},{"id":108500,"name":"Kathleen H. Burns","orcid":"0000-0003-1620-3761","position":8,"is_corresponding":false},{"id":49826,"name":"Jef D. Boeke","orcid":"0000-0001-5322-4946","position":9,"is_corresponding":false},{"id":2222,"name":"David Fenyö","orcid":"0000-0001-5049-3825","position":10,"is_corresponding":false},{"id":446821,"name":"Wilson McKerrow","orcid":"0000-0001-6328-853X","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:21:31.237180Z","pmid":"35169076","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":[]}