ArticleEBioMedicine2016
A Selective Small Molecule DNA2 Inhibitor for Sensitization of Human Cancer Cells to Chemotherapy.
Article in EBioMedicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 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
69 citing papers in PubMed, 99 citations in OpenAlex.
- Activation of Pol theta-mediated end joining begins during mitotic commitment.bioRxiv : the preprint server for biology · 2026Article
- Multi-omics analysis positions DNA2 at the interface of genome integrity programs and tumor behavior in pan-cancer.Functional & integrative genomics · 2026Article
- New selective and allosteric FLT3 inhibitors show efficacy against resistant acute myeloid leukemia cells.iScience · 2026Article
- MDC1 counteracts replication fork reversal and mediates chemosensitivity in BRCA1/2-deficient tumors.Oncogene · 2026Article
- Review
- ATM promotes reversed fork processing during DNA interstrand cross-link repair.bioRxiv : the preprint server for biology · 2025Article
- Article
- DNA2 and MSH2 cooperatively repair stabilized G4 and allow efficient telomere replication.Nature communications · 2025Article
- Article
- DNA double-strand break end resection factors and WRN facilitate mitotic DNA synthesis in human cells.Nature communications · 2025Article
- Discovery and Characterization of Small Molecule Inhibitors Targeting Exonuclease 1 for Homologous Recombination-Deficient Cancer Therapy.ACS chemical biology · 2025Article
- DNA2 and MSH2 activity collectively mediate chemically stabilized G4 for efficient telomere replication.bioRxiv : the preprint server for biology · 2025Article
- Article
- CAF-1 promotes efficient PrimPol recruitment to nascent DNA for single-stranded DNA gap formation.Nucleic acids research · 2024Article
- Identification of Brain Cell Type-Specific Therapeutic Targets for Glioma From Genetics.CNS neuroscience & therapeutics · 2024Article
- Switch-like phosphorylation of WRN integrates end-resection with RAD51 metabolism at collapsed replication forks.Nucleic acids research · 2024Article
- Article
- Structure-specific nucleases in genome dynamics and strategies for targeting cancers.Journal of molecular cell biology · 2024Review
- USP50 suppresses alternative RecQ helicase use and deleterious DNA2 activity during replication.Nature communications · 2024Article
- ATM and 53BP1 regulate alternative end joining-mediated V(D)J recombination.Science advances · 2024Article
9 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
15 authors at 6 institutions in 2 countries.
Funding
Abstract
Cancer cells frequently up-regulate DNA replication and repair proteins such as the multifunctional DNA2 nuclease/helicase, counteracting DNA damage due to replication stress and promoting survival. Therefore, we hypothesized that blocking both DNA replication and repair by inhibiting the bifunctional DNA2 could be a potent strategy to sensitize cancer cells to stresses from radiation or chemotherapeutic agents. We show that homozygous deletion of DNA2 sensitizes cells to ionizing radiation and camptothecin (CPT). Using a virtual high throughput screen, we identify 4-hydroxy-8-nitroquinoline-3-carboxylic acid (C5) as an effective and selective inhibitor of DNA2. Mutagenesis and biochemical analysis define the C5 binding pocket at a DNA-binding motif that is shared by the nuclease and helicase activities, consistent with structural studies that suggest that DNA binding to the helicase domain is necessary for nuclease activity. C5 targets the known functions of DNA2 in vivo: C5 inhibits resection at stalled forks as well as reducing recombination. C5 is an even more potent inhibitor of restart of stalled DNA replication forks and over-resection of nascent DNA in cells defective in replication fork protection, including BRCA2 and BOD1L. C5 sensitizes cells to CPT and synergizes with PARP inhibitors.
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.