ArticlePloS one2013
A genetic screen using the PiggyBac transposon in haploid cells identifies Parp1 as a mediator of olaparib toxicity.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
What it found
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Who cites it
103 citing papers in PubMed, 174 citations in OpenAlex.
- Natural Products as Modulators of the DNA Damage Response and Oncogenic Signaling in Breast Cancer Therapy.International journal of molecular sciences · 2026Review
- Increased efficacy of PARP inhibitors against cisplatin-sensitive and -resistant ovarian cancer cells mediated via ATR and ATM inhibition.Cell death discovery · 2025Article
- [Communications medicine · 2025Article
- Replication Stress Is an Actionable Genetic Vulnerability in Desmoplastic Small Round Cell Tumors.Cancer research · 2025Article
- Emerging opportunities to treat drug-resistant breast cancer: Discovery of novel small-molecule inhibitors against different targets.Frontiers in pharmacology · 2025Review
- Targeting PARP1: A Promising Approach for Next-Generation Poly (ADP-ribose) Polymerase Inhibitors.Current breast cancer reports · 2025Review
- The Landscape of PARP Inhibitors in Solid Cancers.OncoTargets and therapy · 2025Review
- Base editing screens define the genetic landscape of cancer drug resistance mechanisms.Nature genetics · 2024Article
- KAT6A Condensates Impair PARP1 Trapping of PARP Inhibitors in Ovarian Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Development and application of haploid embryonic stem cells.Stem cell research & therapy · 2024Review
- Article
- A Stem-like Patient-Derived Ovarian Cancer Model of Platinum Resistance Reveals Dissociation of Stemness and Resistance.International journal of molecular sciences · 2024Article
- FANCJ promotes PARP1 activity during DNA replication that is essential in BRCA1 deficient cells.Nature communications · 2024Article
- Molecular mechanism of PARP inhibitor resistance.Oncoscience · 2024Review
- A HUWE1 defect causes PARP inhibitor resistance by modulating the BRCA1-∆11q splice variant.Oncogene · 2023Article
- Multi-omics analysis reveals distinct non-reversion mechanisms of PARPi resistance in BRCA1- versus BRCA2-deficient mammary tumors.Cell reports · 2023Article
- Mechanisms of PARP Inhibitor Resistance.Cancer treatment and research · 2023Article
- Identification of genes contributing to cisplatin resistance in osteosarcoma cells.FEBS open bio · 2023Article
- Analysis of matched primary and recurrent BRCA1/2 mutation-associated tumors identifies recurrence-specific drivers.Nature communications · 2022Article
- Opinion: PARP inhibitors in cancer-what do we still need to know?Open biology · 2022Review
43 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Genetic perturbation screens have the potential to dissect a wide range of cellular phenotypes. Such screens have historically been difficult in diploid mammalian cells. The recent derivation of haploid embryonic stem cells provides an opportunity to cause loss of function mutants with a random mutagen in a mammalian cell with a normal genetic background. We describe an approach to genetic screens that exploits the highly active piggyBac transposon in haploid mammalian cells. As an example of haploid transposon (HTP) screening, we apply this approach to identifying determinants of cancer drug toxicity and resistance. In a screen for 6-thioguanine resistance we recovered components of the DNA mismatch repair pathway, a known requirement for toxicity. In a further screen for resistance to the clinical poly(ADP-ribose) polymerase (PARP) inhibitor olaparib we recovered multiple Parp1 mutants. Our results show that olaparib toxicity to normal cells is mediated predominantly via Parp1, and suggest that the clinical side effects of olaparib may be on target. The transposon mutant libraries are stable and can be readily reused to screen other drugs. The screening protocol described has several advantages over other methods such as RNA interference: it is rapid and low cost, and mutations can be easily reverted to establish causality.
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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.