{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Groslambert J"],"funding":["Cancer Research UK","University of Pittsburgh","National Cancer Institute","NCI NIH HHS","National Institutes of Health","Wellcome Trust","Ovarian Cancer Research Alliance","NIGMS NIH HHS","Nemzeti Kutatási Fejlesztési és Innovációs Hivatal"],"pagination":["113113"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10933786"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["42(9)"],"pubmed_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"],"pubmed_title":["The interplay of TARG1 and PARG protects against genomic instability."],"pmcid":["PMC10933786"],"funding_grant_id":["R01CA207209","220107","T32 GM133332","813369","R01262316","210634/Z/18/Z","C35050/A22284","223107","32GM133332","P30 CA047904","K143248","R01 CA207209","22284","101794","210634","S_4211"],"pubmed_authors":["Jansen J","O'Sullivan RJ","Ahel I","Timinszky G","Prokhorova E","Ahel D","Dobbelstein M","Groslambert J","Tromans-Coia C","Giansanti C","Wondisford AR"],"additional_accession":[]},"is_claimable":false,"name":"The interplay of TARG1 and PARG protects against genomic instability.","description":"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.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Sep","modification":"2026-06-29T03:16:31.083Z","creation":"2025-04-06T14:31:57.683Z"},"accession":"S-EPMC10933786","cross_references":{"pubmed":["37676774"],"doi":["10.1016/j.celrep.2023.113113"]}}