{"doi":"10.1016/j.celrep.2023.113113","title":"The interplay of TARG1 and PARG protects against genomic instability","abstract":"The timely removal of ADP-ribosylation is crucial for efficient DNA repair. However, much remains to be discovered about ADP-ribosylhydrolases. Here, we characterize the physiological role of TARG1, an ADP-ribosylhydrolase that removes aspartate/glutamate-linked ADP-ribosylation. We reveal its function in the DNA damage response and show that the loss of TARG1 sensitizes cells to inhibitors of topoisomerase II, ATR, and PARP. Furthermore, we find a PARP1-mediated synthetic lethal interaction between TARG1 and PARG, driven by the toxic accumulation of ADP-ribosylation, that induces replication stress and genomic instability. Finally, we show that histone PARylation factor 1 (HPF1) deficiency exacerbates the toxicity and genomic instability induced by excessive ADP-ribosylation, suggesting a close crosstalk between components of the serine- and aspartate/glutamate-linked ADP-ribosylation pathways. Altogether, our data identify TARG1 as a potential biomarker for the response of cancer cells to PARP and PARG inhibition and establish that the interplay of TARG1 and PARG protects cells against genomic instability.","journal":"Cell Reports","year":2023,"id":329496,"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":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9506,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":635065,"name":"Evgeniia Prokhorova","orcid":"0000-0002-5467-5586","position":1,"is_corresponding":false},{"id":327758,"name":"Anne R. Wondisford","orcid":null,"position":2,"is_corresponding":false},{"id":1052199,"name":"Callum Tromans‐Coia","orcid":"0000-0002-5518-8915","position":3,"is_corresponding":false},{"id":1052200,"name":"Celeste Giansanti","orcid":"0000-0003-3229-8385","position":4,"is_corresponding":false},{"id":1052201,"name":"Jennifer Jansen","orcid":"0000-0001-6993-3069","position":5,"is_corresponding":false},{"id":618543,"name":"Gyula Timinszky","orcid":"0000-0001-6342-8985","position":6,"is_corresponding":false},{"id":1052202,"name":"Matthias Dobbelstein","orcid":"0000-0001-5052-3967","position":7,"is_corresponding":false},{"id":289469,"name":"Dragana Ahel","orcid":"0000-0002-7042-156X","position":8,"is_corresponding":false},{"id":326575,"name":"Roderick J. O’Sullivan","orcid":"0000-0002-0289-0911","position":9,"is_corresponding":false},{"id":117233,"name":"Ivan Ahel","orcid":null,"position":10,"is_corresponding":false},{"id":635069,"name":"Joséphine Groslambert","orcid":"0000-0002-3254-2854","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T01:09:01.509601Z","pmid":"37676774","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":[]}