ArticleeLife2024
DePARylation is critical for S phase progression and cell survival.
Article in eLife, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 12 citations in OpenAlex.
- PARG inhibition reduces ssDNA levels and limits RPA loading upon replication fork collapse.EMBO reports · 2026Article
- CHD1L maintains genome integrity by facilitating okazaki fragment maturation.Nucleic acids research · 2026Article
- Multiple Regulatory Mechanisms of Post-Translational Modifications and Therapeutic Potential of Mitotic Catastrophe.International journal of molecular sciences · 2026Review
- Mutant p53 Directs PARP to Regulate Replication Stress and Drive Breast Cancer Metastasis.bioRxiv : the preprint server for biology · 2026Article
- Poly(ADP-ribose) glycohydrolase enforces p21 degradation via dePARylation to promote gastric cancer progression.The Journal of clinical investigation · 2026Article
- Targeting MARylation and DePARylation in Cancer Therapy: New Promising Therapeutic Opportunities.Cancers · 2025Review
- Replication-associated base excision repair/single-strand break repair regulates PARG inhibitor response via the PRMT1/PRMT5/ATR axis.NAR cancer · 2025Article
- Mechanistic insights into the monotherapy and combination potential of FEN1 inhibition in cancer therapy.Nucleic acids research · 2025Article
- Genetic evidence for PARP1 trapping as a driver of PARP inhibitor efficacy in BRCA mutant cancer cells.Nucleic acids research · 2025Article
- 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
- Joining of DNA breaks- interplay between DNA ligases and poly (ADP-ribose) polymerases.DNA repair · 2025Review
- Suppression of ADP-ribosylation reversal triggers cell vulnerability to alkylating agents.Neoplasia (New York, N.Y.) · 2025Article
- O-GlcNAcylation of RPA2 at S4/S8 antagonizes phosphorylation and regulates checkpoint activation during replication stress.The Journal of biological chemistry · 2024Article
- PARG inhibitor sensitivity correlates with accumulation of single-stranded DNA gaps in preclinical models of ovarian cancer.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- ADP-ribose hydrolases: biological functions and potential therapeutic targets.Expert reviews in molecular medicine · 2024Review
- CHK1 inhibitor induced PARylation by targeting PARG causes excessive replication and metabolic stress and overcomes chemoresistance in ovarian cancer.Cell death discovery · 2024Article
- 1,25-Dihydroxyvitamin DInternational journal of molecular sciences · 2024Article
- OGT and OGA: Sweet guardians of the genome.The Journal of biological chemistry · 2024Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Poly(ADP-ribose)ylation or PARylation by PAR polymerase 1 (PARP1) and dePARylation by poly(ADP-ribose) glycohydrolase (PARG) are equally important for the dynamic regulation of DNA damage response. PARG, the most active dePARylation enzyme, is recruited to sites of DNA damage via pADPr-dependent and PCNA-dependent mechanisms. Targeting dePARylation is considered an alternative strategy to overcome PARP inhibitor resistance. However, precisely how dePARylation functions in normal unperturbed cells remains elusive. To address this challenge, we conducted multiple CRISPR screens and revealed that dePARylation of S phase pADPr by PARG is essential for cell viability. Loss of dePARylation activity initially induced S-phase-specific pADPr signaling, which resulted from unligated Okazaki fragments and eventually led to uncontrolled pADPr accumulation and PARP1/2-dependent cytotoxicity. Moreover, we demonstrated that proteins involved in Okazaki fragment ligation and/or base excision repair regulate pADPr signaling and cell death induced by PARG inhibition. In addition, we determined that PARG expression is critical for cellular sensitivity to PARG inhibition. Additionally, we revealed that PARG is essential for cell survival by suppressing pADPr. Collectively, our data not only identify an essential role for PARG in normal proliferating cells but also provide a potential biomarker for the further development of PARG inhibitors in cancer therapy.
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What OpenQuestion holds
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.