ArticleDNA repair2018
Inhibition of non-homologous end joining in Fanconi Anemia cells results in rescue of survival after interstrand crosslinks but sensitization to replication associated double-strand breaks.
Article in DNA repair, 2018. 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
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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.
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, 29 citations in OpenAlex.
- Discovery of Two Structurally Distinct Classes of Inhibitors Targeting the Nuclease MUS81 and Enhancing Efficacy of Chemotherapy in Cancer Cells.Journal of medicinal chemistry · 2026Article
- A porcine model of Fanconi anemia.PloS one · 2025Article
- Large-scale copy number alterations are enriched for synthetic viability in BRCA1/BRCA2 tumors.Genome medicine · 2024Article
- The Fanconi anemia core complex promotes CtIP-dependent end resection to drive homologous recombination at DNA double-strand breaks.Nature communications · 2024Article
- AZD-7648, a DNA-PK Inhibitor, Induces DNA Damage, Apoptosis, and Cell Cycle Arrest in Chronic and Acute Myeloid Leukemia Cells.International journal of molecular sciences · 2023Article
- Fanconi anemia-associated chromosomal radial formation is dependent on POLθ-mediated alternative end joining.Cell reports · 2023Article
- Identification of a HypomorphicGenes · 2022Article
- DNMT3A Harboring Leukemia-Associated Mutations Directs Sensitivity to DNA Damage at Replication Forks.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Type-I Interferon Signaling in Fanconi Anemia.Frontiers in cellular and infection microbiology · 2022Review
- DDRugging glioblastoma: understanding and targeting the DNA damage response to improve future therapies.Molecular oncology · 2022Review
- DNA damage repair in glioblastoma: current perspectives on its role in tumour progression, treatment resistance and PIKKing potential therapeutic targets.Cellular oncology (Dordrecht, Netherlands) · 2021Review
- Disabling the Fanconi Anemia Pathway in Stem Cells Leads to Radioresistance and Genomic Instability.Cancer research · 2021Article
- MYC Promotes Bone Marrow Stem Cell Dysfunction in Fanconi Anemia.Cell stem cell · 2021Article
- Beta Human Papillomavirus 8E6 Attenuates Non-Homologous End Joining by Hindering DNA-PKcs Activity.Cancers · 2020Article
- Cooperation of the ATM and Fanconi Anemia/BRCA Pathways in Double-Strand Break End Resection.Cell reports · 2020Article
- Poly(ADP-Ribose) Polymerase-3 Regulates Regeneration in Planarians.International journal of molecular sciences · 2020Article
- Fanconi Anemia DNA Repair Pathway as a New Mechanism to Exploit Cancer Drug Resistance.Mini reviews in medicinal chemistry · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
When Fanconi Anemia (FA) proteins were depleted in human U2OS cells with integrated DNA repair reporters, we observed decreases in homologous recombination (HR), decreases in mutagenic non-homologous end joining (m-NHEJ) and increases in canonical NHEJ, which was independently confirmed by measuring V(D)J recombination. Furthermore, depletion of FA proteins resulted in reduced HR protein foci and increased NHEJ protein recruitment to replication-associated DSBs, consistent with our observation that the use of canonical NHEJ increases after depletion of FA proteins in cycling cells. FA-depleted cells and FA-mutant cells were exquisitely sensitive to a DNA-PKcs inhibitor (DNA-PKi) after sustaining replication-associated double strand breaks (DSBs). By contrast, after DNA interstrand crosslinks, DNA-PKi resulted in increased survival in FA-deficient cells, implying that NHEJ is contributing to lethality after crosslink repair. Our results suggest FA proteins inhibit NHEJ, since repair intermediates from crosslinks are rendered lethal by NHEJ. The implication is that bone marrow failure in FA could be triggered by naturally occurring DNA crosslinks, and DNA-PK inhibitors would be protective. Since some sporadic cancers have been shown to have deficiencies in the FA-pathway, these tumors should be vulnerable to NHEJ inhibitors with replication stress, but not with crosslinking agents, which could be tested in future clinical trials.
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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.