ArticleCell death & disease2013
PARG dysfunction enhances DNA double strand break formation in S-phase after alkylation DNA damage and augments different cell death pathways.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 66 citations in OpenAlex.
- The Expanding Landscape of ADP-Ribosylation: Protein, DNA, RNA, and Mitochondrial Regulation.Chemical research in toxicology · 2026Review
- 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
- Angiopoietin-like protein 8 directs DNA damage responses towards apoptosis by stabilizing PARP1-DNA condensates.Cell death and differentiation · 2025Article
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- The interplay of TARG1 and PARG protects against genomic instability.Cell reports · 2023Article
- Alkylation of nucleobases by 2-chloro-NAR cancer · 2023Article
- Extracellular Leakage Protein Patterns in Two Types of Cancer Cell Death: Necrosis and Apoptosis.ACS omega · 2023Article
- PARPs and ADP-ribosylation: Deciphering the complexity with molecular tools.Molecular cell · 2023Review
- Molecular Mechanisms of Parthanatos and Its Role in Diverse Diseases.International journal of molecular sciences · 2022Review
- Therapeutic resistance in pancreatic ductal adenocarcinoma: Current challenges and future opportunities.World journal of gastroenterology · 2021Review
- ADP-ribosylhydrolases: from DNA damage repair to COVID-19.Journal of Zhejiang University. Science. B · 2021Review
- The Making and Breaking of Serine-ADP-Ribosylation in the DNA Damage Response.Frontiers in cell and developmental biology · 2021Review
- Poly(ADP-ribose) Glycohydrolase Inhibition Sequesters NADCancer discovery · 2020Article
- AI26 inhibits the ADP-ribosylhydrolase ARH3 and suppresses DNA damage repair.The Journal of biological chemistry · 2020Article
- Reduced Tumorigenicity of Mouse ES Cells and the Augmented Anti-Tumor Therapeutic Effects underCancers · 2020Article
- Therapeutic Strategies and Biomarkers to Modulate PARP Activity for Targeted Cancer Therapy.Cancers · 2020Review
- DNA methylation-mediated repression of exosomal miR-652-5p expression promotes oesophageal squamous cell carcinoma aggressiveness by targeting PARG and VEGF pathways.PLoS genetics · 2020Article
- Androgen Receptor and Poly(ADP-ribose) Glycohydrolase Inhibition Increases Efficiency of Androgen Ablation in Prostate Cancer Cells.Scientific reports · 2020Article
- PARP and PARG inhibitors in cancer treatment.Genes & development · 2020Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Poly(ADP-ribose) glycohydrolase (PARG) is the primary enzyme responsible for the degradation of poly(ADP-ribose). PARG dysfunction sensitizes cells to alkylating agents and induces cell death; however, the details of this effect have not been fully elucidated. Here, we investigated the mechanism by which PARG deficiency leads to cell death in different cell types using methylmethanesulfonate (MMS), an alkylating agent, and Parg(-/-) mouse ES cells and human cancer cell lines. Parg(-/-) mouse ES cells showed increased levels of γ-H2AX, a marker of DNA double strand breaks (DSBs), accumulation of poly(ADP-ribose), p53 network activation, and S-phase arrest. Early apoptosis was enhanced in Parg(-/-) mouse ES cells. Parg(-/-) ES cells predominantly underwent caspase-dependent apoptosis. PARG was then knocked down in a p53-defective cell line, MIAPaCa2 cells, a human pancreatic cancer cell line. MIAPaCa2 cells were sensitized to MMS by PARG knockdown. Enhanced necrotic cell death was induced in MIAPaCa2 cells after augmenting γ-H2AX levels and S-phase arrest. Taken together, these data suggest that DSB repair defect causing S-phase arrest, but p53 status was not important for sensitization to alkylation DNA damage by PARG dysfunction, whereas the cell death pathway is dependent on the cell type. This study demonstrates that functional inhibition of PARG may be useful for sensitizing at least particular cancer cells to alkylating agents.
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