{"doi":"10.1073/pnas.2116254119","title":"The UVSSA protein is part of a genome integrity homeostasis network with links to transcription-coupled DNA repair and ATM signaling","abstract":"SignificanceTranscription-coupled repair (TCR) involves four core proteins: CSA, CSB, USP7, and UVSSA. CSA and CSB are mutated in the severe human neurocutaneous disease Cockayne syndrome. In contrast UVSSA is a mild photosensitive disease in which a mutated protein sequence prevents recruitment of USP7 protease to deubiquitinate and stabilize CSB. We deleted the UVSSA protein using CRISPR-Cas9 in an aneuploid cell line, HEK293, and determined the functional consequences. The knockout cell line was sensitive to transcription-blocking lesions but not sensitive to oxidative agents or PARP inhibitors, unlike CSB. Knockout of UVSSA also activated ATM, like CSB, in transcription-arrested cells. The phenotype of UVSSA, especially its rarity, suggests that many TCR-deficient patients and tumors fail to be recognized clinically.","journal":"Proceedings of the National Academy of Sciences","year":2022,"id":283261,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9424,"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":94243,"name":"Sarah T. Arron","orcid":"0000-0001-5669-0627","position":1,"is_corresponding":false},{"id":94245,"name":"James E. Cleaver","orcid":"0000-0003-4360-6750","position":2,"is_corresponding":false},{"id":723440,"name":"Vladimir Bezrookove","orcid":"0000-0002-8291-6877","position":3,"is_corresponding":false},{"id":960123,"name":"Deneb Karentz","orcid":null,"position":4,"is_corresponding":false},{"id":264060,"name":"Brian Lu","orcid":"0000-0002-6381-5499","position":5,"is_corresponding":false},{"id":576870,"name":"Eli Perr","orcid":"0000-0003-4791-3985","position":6,"is_corresponding":false},{"id":264374,"name":"Darwin Chang","orcid":"0000-0001-5635-9109","position":7,"is_corresponding":false},{"id":311032,"name":"Thoru Pederson","orcid":"0000-0002-3703-7806","position":8,"is_corresponding":false},{"id":960122,"name":"Magdalena Kordon","orcid":null,"position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:29:23.777809Z","pmid":"35254895","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":[]}