ArticleNucleic acids research2021
Genome-wide CRISPR screens reveal cyclin C as synthetic survival target of BRCA2.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- AI-driven CRISPR strategies in breast cancer: Organoid modeling, adaptive editing, and precision delivery.Iranian journal of basic medical sciences · 2026Review
- USP37 counteracts HLTF to protect damaged replication forks and promote survival of BRCA1-deficient cells and PARP inhibitor resistance.Nucleic acids research · 2025Article
- Synthetic lethal strategies for the development of cancer therapeutics.Nature reviews. Clinical oncology · 2025Review
- FACS-based genome-wide CRISPR screening platform identifies modulators of CD47.Frontiers in immunology · 2025Article
- Ovarian cancer targeted therapy: current landscape and future challenges.Frontiers in oncology · 2025Review
- Large-scale copy number alterations are enriched for synthetic viability in BRCA1/BRCA2 tumors.Genome medicine · 2024Article
- Systematic investigation of BRCA1-A, -B, and -C complexes and their functions in DNA damage response and DNA repair.Oncogene · 2024Article
- Genome-wide CRISPR screen reveals the synthetic lethality between BCL2L1 inhibition and radiotherapy.Life science alliance · 2024Article
- EXO1 protects BRCA1-deficient cells against toxic DNA lesions.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
- CRISPR/Cas9-Mediated Genome Editing in Cancer Therapy.International journal of molecular sciences · 2023Review
- Revolutionizing DNA repair research and cancer therapy with CRISPR-Cas screens.Nature reviews. Molecular cell biology · 2023Review
- Transcriptional Antagonism by CDK8 Inhibition Improves Therapeutic Efficacy of MEK Inhibitors.Cancer research · 2023Article
- PICKLES v3: the updated database of pooled in vitro CRISPR knockout library essentiality screens.Nucleic acids research · 2023Article
- Article
- A CRISPR Path to Finding Vulnerabilities and Solving Drug Resistance: Targeting the Diverse Cancer Landscape and Its Ecosystem.Advanced genetics (Hoboken, N.J.) · 2022Review
- TMEM158 promotes the proliferation and migration of glioma cells via STAT3 signaling in glioblastomas.Cancer gene therapy · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Poly (ADP-ribose) polymerase inhibitor (PARPi)-based therapies initially reduce tumor burden but eventually lead to acquired resistance in cancer patients with BRCA1 or BRCA2 mutation. To understand the potential PARPi resistance mechanisms, we performed whole-genome CRISPR screens to discover genetic alterations that change the gene essentiality in cells with inducible depletion of BRCA2. We identified that several RNA Polymerase II transcription Mediator complex components, especially Cyclin C (CCNC) as synthetic survival targets upon BRCA2 loss. Total mRNA sequencing demonstrated that loss of CCNC could activate the transforming growth factor (TGF)-beta signaling pathway and extracellular matrix (ECM)-receptor interaction pathway, however the inhibition of these pathways could not reverse cell survival in BRCA2 depleted CCNC-knockout cells, indicating that the activation of these pathways is not required for the resistance. Moreover, we showed that the improved survival is not due to restoration of homologous recombination repair although decreased DNA damage signaling was observed. Interestingly, loss of CCNC could restore replication fork stability in BRCA2 deficient cells, which may contribute to PARPi resistance. Taken together, our data reveal CCNC as a critical genetic determinant upon BRCA2 loss of function, which may help the development of novel therapeutic strategies that overcome PARPi resistance.
Indexed as
Identifiers
What OpenQuestion holds
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.