ArticleMolecular cell2020
Endogenous DNA 3' Blocks Are Vulnerabilities for BRCA1 and BRCA2 Deficiency and Are Reversed by the APE2 Nuclease.
Article in Molecular cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 115 citations in OpenAlex.
- Finding novel vulnerabilities of hypomorphic BRCA1 alleles.Molecular oncology · 2026Article
- Analysis of Combinatorial Knockout CRISPR Screens with GRAPE: Genetic interaction Regression Analysis of Pairwise Effects.bioRxiv : the preprint server for biology · 2026Article
- Exploiting synthetic lethality in epithelial ovarian cancer: multi-dimensional approaches beyond DNA damage repair.Molecular cancer · 2026Review
- A Chemical-Genetic Interaction Matrix Reveals Drug Mechanism and Genetic Architecture.bioRxiv : the preprint server for biology · 2026Article
- Uncovering genetic interactions in the DNA repair network in response to endogenous damage and ionizing radiation.Cell reports · 2026Article
- Functional modules predict cancer-relevant genetic interactions in mammalian cells.bioRxiv : the preprint server for biology · 2025Article
- 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
- BRCA1 and BRCA2: from cancer susceptibility to synthetic lethality.Genes & development · 2025Review
- Synthetic lethal strategies for the development of cancer therapeutics.Nature reviews. Clinical oncology · 2025Review
- A multilineage screen identifies actionable synthetic lethal interactions in human cancers.Nature genetics · 2025Article
- Differential PARP inhibitor responses in BRCA1-deficient and resistant cells in competitive co-culture.PloS one · 2025Article
- Recombinant Topoisomerase 2 Production Using Cultured Human Cell Lines.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Structure-specific nucleases in genome dynamics and strategies for targeting cancers.Journal of molecular cell biology · 2024Review
- The Fanconi anemia pathway induces chromothripsis and ecDNA-driven cancer drug resistance.Cell · 2024Article
- From the TOP: Formation, recognition and resolution of topoisomerase DNA protein crosslinks.DNA repair · 2024Review
- Endogenous base damage as a driver of genomic instability in homologous recombination-deficient cancers.DNA repair · 2024Review
- DNA abasic sites act as rational therapeutic targets to synergize temozolomide response in both MMR-proficient and deficient cancer.NAR cancer · 2024Review
- Large-scale copy number alterations are enriched for synthetic viability in BRCA1/BRCA2 tumors.Genome medicine · 2024Article
- Serum Extracellular Vesicles Cargo Approach in Bitches with Mammary Tumors.Current issues in molecular biology · 2024Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 4 institutions in 3 countries.
Funding
Abstract
The APEX2 gene encodes APE2, a nuclease related to APE1, the apurinic/apyrimidinic endonuclease acting in base excision repair. Loss of APE2 is lethal in cells with mutated BRCA1 or BRCA2, making APE2 a prime target for homologous recombination-defective cancers. However, because the function of APE2 in DNA repair is poorly understood, it is unclear why BRCA-deficient cells require APE2 for viability. Here we present the genetic interaction profiles of APE2, APE1, and TDP1 deficiency coupled to biochemical and structural dissection of APE2. We conclude that the main role of APE2 is to reverse blocked 3' DNA ends, problematic lesions that preclude DNA synthesis. Our work also suggests that TOP1 processing of genomic ribonucleotides is the main source of 3'-blocking lesions relevant to APEX2-BRCA1/2 synthetic lethality. The exquisite sensitivity of BRCA-deficient cells to 3' blocks indicates that they represent a tractable vulnerability in homologous recombination-deficient tumor cells.
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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.