ArticleCell cycle (Georgetown, Tex.)2015
Replication-induced DNA damage after PARP inhibition causes G2 delay, and cell line-dependent apoptosis, necrosis and multinucleation.
Article in Cell cycle (Georgetown, Tex.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 53 citations in OpenAlex.
- Synthetic lethality between PBRM1 deficiency and PARP inhibitors: exploiting G2/M checkpoint arrest in colorectal cancer.Molecular medicine (Cambridge, Mass.) · 2026Article
- Mitochondrial superoxide sustains a senescence-like phenotype in PARP- inhibited ovarian cancer cells by stabilizing HIF1α.Redox biology · 2026Article
- CDK12/CDK13 inhibition disrupts transcriptional elongation and replication fork progression in glioblastoma.EMBO molecular medicine · 2026Article
- N4-acetylcytidine and other RNA modifications in epitranscriptome: insight into DNA repair and cancer development.Epigenomics · 2025Review
- Role of BRCA1 in glioblastoma etiology.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- A synthetic lethal dependency on casein kinase 2 in response to replication-perturbing therapeutics in RB1-deficient cancer cells.Science advances · 2024Article
- Article
- Inhibition of nicotinamide dinucleotide salvage pathway counters acquired and intrinsic poly(ADP-ribose) polymerase inhibitor resistance in high-grade serous ovarian cancer.Scientific reports · 2023Article
- Diaporine Potentiates the Anticancer Effects of Oxaliplatin and Doxorubicin on Liver Cancer Cells.Journal of personalized medicine · 2022Article
- Current Treatments and New Possible Complementary Therapies for Epithelial Ovarian Cancer.Biomedicines · 2021Review
- Metformin Affects Olaparib Sensitivity through Induction of Apoptosis in Epithelial Ovarian Cancer Cell Lines.International journal of molecular sciences · 2021Article
- Alternative models of cancer stem cells: The stemness phenotype model, 10 years later.World journal of stem cells · 2021Review
- Combination of Talazoparib and Palbociclib as a Potent Treatment Strategy in Bladder Cancer.Journal of personalized medicine · 2021Article
- The SC-35 Splicing Factor Interacts with RNA Pol II and A-Type Lamin Depletion Weakens This Interaction.Cells · 2021Article
- PARP and PARG inhibitors in cancer treatment.Genes & development · 2020Review
- Development of a Hyaluronic Acid-Based Nanocarrier Incorporating Doxorubicin and Cisplatin as a pH-Sensitive and CD44-Targeted Anti-Breast Cancer Drug Delivery System.Frontiers in pharmacology · 2020Article
- Premature mitotic entry induced by ATR inhibition potentiates olaparib inhibition-mediated genomic instability, inflammatory signaling, and cytotoxicity in BRCA2-deficient cancer cells.Molecular oncology · 2019Article
- Combined poly-ADP ribose polymerase and ataxia-telangiectasia mutated/Rad3-related inhibition targets ataxia-telangiectasia mutated-deficient lung cancer cells.British journal of cancer · 2019Article
- Mitotic functions of poly(ADP-ribose) polymerases.Biochemical pharmacology · 2019Review
- A CEP104-CSPP1 Complex Is Required for Formation of Primary Cilia Competent in Hedgehog Signaling.Cell reports · 2019Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PARP inhibitors have been approved for treatment of tumors with mutations in or loss of BRCA1/2. The molecular mechanisms and particularly the cellular phenotypes resulting in synthetic lethality are not well understood and varying clinical responses have been observed. We have investigated the dose- and time-dependency of cell growth, cell death and cell cycle traverse of 4 malignant lymphocyte cell lines treated with the PARP inhibitor Olaparib. PARP inhibition induced a severe growth inhibition in this cell line panel and increased the levels of phosphorylated H2AX-associated DNA damage in S phase. Repair of the remaining replication related damage caused a G2 phase delay before entry into mitosis. The G2 delay, and the growth inhibition, was more pronounced in the absence of functional ATM. Further, Olaparib treated Reh and Granta-519 cells died by apoptosis, while U698 and JVM-2 cells proceeded through mitosis with aberrant chromosomes, skipped cytokinesis, and eventually died by necrosis. The TP53-deficient U698 cells went through several rounds of DNA replication and mitosis without cytokinesis, ending up as multinucleated cells with DNA contents of up to 16c before dying. In summary, we report here for the first time cell cycle-resolved DNA damage induction, and cell line-dependent differences in the mode of cell death caused by PARP inhibition.
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