ArticleMolecular cell2019
Genetic Screens Reveal FEN1 and APEX2 as BRCA2 Synthetic Lethal Targets.
Article in Molecular cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers.
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Who cites it
139 citing papers in PubMed, 195 citations in OpenAlex.
- PCNA-RECQL5-RPRD1B recruit repair components to stressed replication forks to promote survival of BRCA1-deficient cancer cells.Nucleic acids research · 2026Article
- Disruption of microhomology-mediated end joining in Ewing sarcoma.Molecular cell · 2026Article
- Defective microhomology-mediated end joining inScience advances · 2026Article
- Two distinct Okazaki fragment failure modes dominate mutagenesis in the absence of flap endonuclease 1.Nature communications · 2026Article
- Context-dependent synthetic lethality - an emerging precision therapeutic approach.Nature reviews. Cancer · 2026Review
- A RHNO1-ATR/Chk1 positive feedback loop sustains the DNA replication stress response.bioRxiv : the preprint server for biology · 2026Article
- Review
- CRISPR technology in ovarian cancer research: advances from gene editing to precision diagnosis and therapy.Translational cancer research · 2026Review
- Exploiting synthetic lethality in epithelial ovarian cancer: multi-dimensional approaches beyond DNA damage repair.Molecular cancer · 2026Review
- Uncovering genetic interactions in the DNA repair network in response to endogenous damage and ionizing radiation.Cell reports · 2026Article
- Synthetic lethality in cancer drug discovery: challenges and opportunities.Nature reviews. Drug discovery · 2026Review
- Rotenone Inhibited Osteosarcoma Cell Growth Through USP47-Induced Decreases in FEN1 Stability and DNA Integrity.Drug design, development and therapy · 2026Article
- Emerging insights into alternative end‑joining: Mechanisms, genome instability and therapeutic opportunities in cancer (Review).International journal of oncology · 2025Review
- Contrasting roles of APE1 and APE2 in genome maintenance, cancer development, and therapeutic targeting.NAR cancer · 2025Review
- Mechanistic insights into the monotherapy and combination potential of FEN1 inhibition in cancer therapy.Nucleic acids research · 2025Article
- Defective Microhomology-Mediated End-joining in SMARCB1-Deficient Tumors.bioRxiv : the preprint server for biology · 2025Article
- The 9-1-1 complex protects ssDNA gaps in BRCA2-deficient cancer.bioRxiv : the preprint server for biology · 2025Article
- Revealing genetic drivers of ovarian cancer and chemoresistance: insights from whole-genome CRISPR-knockout library screens.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Disruption of Microhomology-mediated End-joining in Ewing Sarcoma.bioRxiv : the preprint server for biology · 2025Article
- Exploring the Potential of Homologous Recombination Protein PALB2 in Synthetic Lethal Combinations.ACS chemical biology · 2025Article
79 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
BRCA1 or BRCA2 inactivation drives breast and ovarian cancer but also creates vulnerability to poly(ADP-ribose) polymerase (PARP) inhibitors. To search for additional targets whose inhibition is synthetically lethal in BRCA2-deficient backgrounds, we screened two pairs of BRCA2 isogenic cell lines with DNA-repair-focused small hairpin RNA (shRNA) and CRISPR (clustered regularly interspaced short palindromic repeats)-based libraries. We found that BRCA2-deficient cells are selectively dependent on multiple pathways including base excision repair, ATR signaling, and splicing. We identified APEX2 and FEN1 as synthetic lethal genes with both BRCA1 and BRCA2 loss of function. BRCA2-deficient cells require the apurinic endonuclease activity and the PCNA-binding domain of Ape2 (APEX2), but not Ape1 (APEX1). Furthermore, BRCA2-deficient cells require the 5' flap endonuclease but not the 5'-3' exonuclease activity of Fen1, and chemically inhibiting Fen1 selectively targets BRCA-deficient cells. Finally, we developed a microhomology-mediated end-joining (MMEJ) reporter and showed that Fen1 participates in MMEJ, underscoring the importance of MMEJ as a collateral repair pathway in the context of homologous recombination (HR) deficiency.
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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.