ArticleNature communications2016
Synthetic viability by BRCA2 and PARP1/ARTD1 deficiencies.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 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
89 citing papers in PubMed, 138 citations in OpenAlex.
- Resistance to neoadjuvant talazoparib in triple-negative breast cancer by BRN2-induced ATR/STAT3 pathways or SHLD2 subclone expansion.Proceedings of the National Academy of Sciences of the United States of America · 2026Trial
- GiGCN: a network-based framework for uncovering synthetic lethal and viable genetic interactions.Briefings in bioinformatics · 2026Article
- RAD51 in Breast Cancer: From Vulnerability to Resistance.World journal of oncology · 2026Review
- Decoding replication stress responses through post-translational modifications.Nature chemical biology · 2025Review
- Dual Inhibition of PARP and Akt Induces Metabolic Collapse and Apoptosis in Breast Cancer Cells.Cancers · 2025Article
- MLKL PARylation in the endothelial niche triggers angiocrine necroptosis to evade cancer immunosurveillance and chemotherapy.Nature cell biology · 2025Article
- Unraveling the nexus: Genomic instability and metabolism in cancer.Cell reports · 2025Review
- RECQL4 requires PARP1 for recruitment to DNA damage, and PARG dePARylation facilitates its associated role in end joining.Experimental & molecular medicine · 2025Article
- BRCA1 and BRCA2: from cancer susceptibility to synthetic lethality.Genes & development · 2025Review
- UFL1 triggers replication fork degradation by MRE11 in BRCA1/2-deficient cells.Nature chemical biology · 2024Article
- Large-scale copy number alterations are enriched for synthetic viability in BRCA1/BRCA2 tumors.Genome medicine · 2024Article
- PARP1 UFMylation ensures the stability of stalled replication forks.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Surviving without BRCA2: MLH1 gets R-looped in to curtail genomic instability.The Journal of clinical investigation · 2024Article
- BRCA2 promotes genomic integrity and therapy resistance primarily through its role in homology-directed repair.Molecular cell · 2024Article
- PP2A inhibition causes synthetic lethality in BRCA2-mutated prostate cancer models via spindle assembly checkpoint reactivation.The Journal of clinical investigation · 2024Article
- How to sensitize glioblastomas to temozolomide chemotherapy: a gap-centered view.Frontiers in cell and developmental biology · 2024Review
- Multifaceted Role of PARP1 in Maintaining Genome Stability Through Its Binding to Alternative DNA Structures.Journal of molecular biology · 2024Review
- Structural basis for stabilisation of the RAD51 nucleoprotein filament by BRCA2.Nature communications · 2023Article
- Interferon restores replication fork stability and cell viability in BRCA-defective cells via ISG15.Nature communications · 2023Article
- Homologous recombination deficiency derived from whole-genome sequencing predicts platinum response in triple-negative breast cancers.Nature communications · 2023Article
29 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 5 institutions in 1 country.
Funding
Abstract
Poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) olaparib has been approved for treatment of advanced ovarian cancer associated with BRCA1 and BRCA2 mutations. BRCA1- and BRCA2-mutated cells, which are homologous recombination (HR) deficient, are hypersensitive to PARPi through the mechanism of synthetic lethality. Here we examine the effect of PARPi on HR-proficient cells. Olaparib pretreatment, PARP1 knockdown or Parp1 heterozygosity of Brca2(cko/ko) mouse embryonic stem cells (mESCs), carrying a null (ko) and a conditional (cko) allele of Brca2, results in viable Brca2(ko/ko) cells. PARP1 deficiency does not restore HR in Brca2(ko/ko) cells, but protects stalled replication forks from MRE11-mediated degradation through its impaired recruitment. The functional consequence of Parp1 heterozygosity on BRCA2 loss is demonstrated by a significant increase in tumorigenesis in Brca2(cko/cko) mice. Thus, while olaparib efficiently kills BRCA2-deficient cells, we demonstrate that it can also contribute to the synthetic viability if PARP is inhibited before BRCA2 loss.
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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.