ArticleScientific reports2018
Detection of functional protein domains by unbiased genome-wide forward genetic screening.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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
12 citing papers in PubMed, 20 citations in OpenAlex.
- Genetic evidence for PARP1 trapping as a driver of PARP inhibitor efficacy in BRCA mutant cancer cells.Nucleic acids research · 2025Article
- Base editing screens define the genetic landscape of cancer drug resistance mechanisms.Nature genetics · 2024Article
- The Clinical Implications of Reversions in Patients with Advanced Pancreatic Cancer and Pathogenic Variants in BRCA1, BRCA2, or PALB2 after Progression on Rucaparib.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Nimbolide targets RNF114 to induce the trapping of PARP1 and synthetic lethality inScience advances · 2023Article
- PARP1 inhibitors induce pyroptosis via caspase 3-mediated gasdermin E cleavage.Biochemical and biophysical research communications · 2023Article
- Mechanisms of PARP Inhibitor Resistance.Cancer treatment and research · 2023Article
- PARP inhibitors in ovarian cancer: overcoming resistance with combination strategies.Journal of gynecologic oncology · 2022Review
- Preventing and Overcoming Resistance to PARP Inhibitors: A Focus on the Clinical Landscape.Cancers · 2021Review
- PARP1 inhibitors trigger innate immunity via PARP1 trapping-induced DNA damage response.eLife · 2020Article
- Article
- Derivation and maintenance of mouse haploid embryonic stem cells.Nature protocols · 2019Article
- Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance.Nature communications · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Establishing genetic and chemo-genetic interactions has played key roles in elucidating mechanisms by which certain chemicals perturb cellular functions. In contrast to gene disruption/depletion strategies to identify mechanisms of drug resistance, searching for point-mutational genetic suppressors that can identify separation- or gain-of-function mutations has been limited. Here, by demonstrating its utility in identifying chemical-genetic suppressors of sensitivity to the DNA topoisomerase I poison camptothecin or the poly(ADP-ribose) polymerase inhibitor olaparib, we detail an approach allowing systematic, large-scale detection of spontaneous or chemically-induced suppressor mutations in yeast or haploid mammalian cells in a short timeframe, and with potential applications in other haploid systems. In addition to applications in molecular biology research, this protocol can be used to identify drug targets and predict drug-resistance mechanisms. Mapping suppressor mutations on the primary or tertiary structures of protein suppressor hits provides insights into functionally relevant protein domains. Importantly, we show that olaparib resistance is linked to missense mutations in the DNA binding regions of PARP1, but not in its catalytic domain. This provides experimental support to the concept of PARP1 trapping on DNA as the prime source of toxicity to PARP inhibitors, and points to a novel olaparib resistance mechanism with potential therapeutic implications.
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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.