ArticleCell reports2023
The interplay of TARG1 and PARG protects against genomic instability.
Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 17 citations in OpenAlex.
- FET proteins and PARylation-dependent condensates promote replication fork reversal and genome stability.Nature communications · 2026Article
- The Expanding Landscape of ADP-Ribosylation: Protein, DNA, RNA, and Mitochondrial Regulation.Chemical research in toxicology · 2026Review
- Chemical Synthesis of Native ADP-Ribosylated Oligonucleotides Enables Analysis of DNA ADP-Ribosylation Hydrolase Specificity.Journal of the American Chemical Society · 2026Article
- PARG regulates the proteasomal degradation of TARG1.Cell reports · 2026Article
- Overcoming Resistance to PARP Inhibitors in BRCA-Mutated Cancers: Mechanisms and Therapeutic Strategies.Journal of Cancer · 2026Review
- Ubiquitin pathway blockade reveals endogenous ADP-ribosylation marking PARP7 and AHR for degradation.The EMBO journal · 2026Article
- Targeting MARylation and DePARylation in Cancer Therapy: New Promising Therapeutic Opportunities.Cancers · 2025Review
- Histone PARylation factor 1: a review of its role in the DNA damage response.Nucleic acids research · 2025Review
- Poly (ADP-Ribose) Glycohydrolase-Dependent dePARylation of PCNA Is Essential for DNA Replication.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Prospects for PARG inhibitors in cancer therapy.Journal of molecular cell biology · 2025Review
- RECQL4 requires PARP1 for recruitment to DNA damage, and PARG dePARylation facilitates its associated role in end joining.Experimental & molecular medicine · 2025Article
- Suppression of ADP-ribosylation reversal triggers cell vulnerability to alkylating agents.Neoplasia (New York, N.Y.) · 2025Article
- ADP-ribose hydrolases: biological functions and potential therapeutic targets.Expert reviews in molecular medicine · 2024Review
- Review
- PARP14 and PARP9/DTX3L regulate interferon-induced ADP-ribosylation.The EMBO journal · 2024Article
- Deregulated DNA ADP-ribosylation impairs telomere replication.Nature structural & molecular biology · 2024Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.