ArticleProceedings of the National Academy of Sciences of the United States of America2012
Differential effects of poly(ADP-ribose) polymerase inhibition on DNA break repair in human cells are revealed with Epstein-Barr virus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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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
25 citing papers in PubMed, 44 citations in OpenAlex.
- A Phase 2, Single Arm Study of Iniparib in Patients With BRCA1 or BRCA2 Associated Advanced Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer.International journal of gynecological cancer : official journal of the International Gynecological Cancer Society · 2016Trial
- Global Proteomic Determination of the Poly-Pharmacological Effects of PARP Inhibitors Following Treatment of High-Grade Serous Ovarian Cancer Cells.International journal of molecular sciences · 2025Article
- Combined PARP inhibitors and small molecular inhibitors in solid tumor treatment (Review).International journal of oncology · 2023Review
- Niraparib Suppresses Cholangiocarcinoma Tumor Growth by Inducing Oxidative and Replication Stress.Cancers · 2021Article
- Differences in PARP Inhibitors for the Treatment of Ovarian Cancer: Mechanisms of Action, Pharmacology, Safety, and Efficacy.International journal of molecular sciences · 2021Review
- Sweet Melody or Jazz? Transcription Around DNA Double-Strand Breaks.Frontiers in molecular biosciences · 2021Review
- DNA Double-Strand Breaks: A Double-Edged Sword for Trypanosomatids.Frontiers in cell and developmental biology · 2021Review
- The kinase polypharmacology landscape of clinical PARP inhibitors.Scientific reports · 2020Article
- Recent advances in phenotypic drug discovery.F1000Research · 2020Review
- Studying DNA Double-Strand Break Repair: An Ever-Growing Toolbox.Frontiers in molecular biosciences · 2020Review
- ALDH1A1 Contributes to PARP Inhibitor Resistance via Enhancing DNA Repair in BRCA2Molecular cancer therapeutics · 2020Article
- Poly(ADP-ribose) polymerase 1 (PARP1) promotes oxidative stress-induced association of Cockayne syndrome group B protein with chromatin.The Journal of biological chemistry · 2018Article
- Article
- Recombinational repair of radiation-induced double-strand breaks occurs in the absence of extensive resection.Nucleic acids research · 2016Article
- TACC3 deregulates the DNA damage response and confers sensitivity to radiation and PARP inhibition.Oncogene · 2015Article
- Polymorphism within the distal RAD51 gene promoter is associated with colorectal cancer in a Polish population.International journal of clinical and experimental pathology · 2015Article
- DNA damage of glioblastoma multiform cells induced by Beta radiation of iodine-131 in the presence or absence of topotecan: a picogreen and colonogenic assay.Cell journal · 2015Article
- Sources of DNA double-strand breaks and models of recombinational DNA repair.Cold Spring Harbor perspectives in biology · 2014Review
- Linking off-target kinase pharmacology to the differential cellular effects observed among PARP inhibitors.Oncotarget · 2014Article
- Minor grove binding ligands disrupt PARP-1 activation pathways.Oncotarget · 2014Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Poly(ADP-ribose) polymerase (PARP) inhibitors can generate synthetic lethality in cancer cells defective in homologous recombination. However, the mechanism(s) by which they affect DNA repair has not been established. Here we directly determined the effects of PARP inhibition and PARP1 depletion on the repair of ionizing radiation-induced single- and double-strand breaks (SSBs and DSBs) in human lymphoid cell lines. To do this, we developed an in vivo repair assay based on large endogenous Epstein-Barr virus (EBV) circular episomes. The EBV break assay provides the opportunity to assess quantitatively and simultaneously the induction and repair of SSBs and DSBs in human cells. Repair was efficient in G1 and G2 cells and was not dependent on functional p53. shRNA-mediated knockdown of PARP1 demonstrated that the PARP1 protein was not essential for SSB repair. Among 10 widely used PARP inhibitors, none affected DSB repair, although an inhibitor of DNA-dependent protein kinase was highly effective at reducing DSB repair. Only Olaparib and Iniparib, which are in clinical cancer therapy trials, as well as 4-AN inhibited SSB repair. However, a decrease in PARP1 expression reversed the ability of Iniparib to reduce SSB repair. Because Iniparib disrupts PARP1-DNA binding, the mechanism of inhibition does not appear to involve trapping PARP at SSBs.
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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.