ArticleJournal of cell science2019
Repair-independent functions of DNA-PKcs protect irradiated cells from mitotic slippage and accelerated senescence.
Article in Journal of cell science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 24 citations in OpenAlex.
- Numb mitigates intestinal epithelial cell senescence induced by radiation through a PLK1-dependent pathway.Scientific reports · 2026Article
- Review
- Article
- Drug Discovery Targeting Post-Translational Modifications in Response to DNA Damages Induced by Space Radiation.International journal of molecular sciences · 2023Review
- Live-cell tracking of γ-H2AX kinetics reveals the distinct modes of ATM and DNA-PK in the immediate response to DNA damage.Journal of cell science · 2023Article
- DNA double-strand break end synapsis by DNA loop extrusion.Nature communications · 2023Article
- Targeting telomerase reverse transcriptase with the covalent inhibitor NU-1 confers immunogenic radiation sensitization.Cell chemical biology · 2022Article
- The importance of DNAPKcs for blunt DNA end joining is magnified when XLF is weakened.Nature communications · 2022Article
- DNA-PKcs: A Targetable Protumorigenic Protein Kinase.Cancer research · 2022Review
- DCLK1 promotes colorectal cancer stemness and aggressiveness via the XRCC5/COX2 axis.Theranostics · 2022Article
- TdT-dUTP DSB End Labeling (TUDEL), for Specific, Direct In Situ Labeling of DNA Double Strand Breaks.Methods in molecular biology (Clifton, N.J.) · 2022Article
- An in vivo genome-wide shRNA screen identifies BCL6 as a targetable biomarker of paclitaxel resistance in breast cancer.Molecular oncology · 2021Article
- An ATM-Chk2-INCENP pathway activates the abscission checkpoint.The Journal of cell biology · 2021Article
- Review
- Nocodazole-Induced Expression and Phosphorylation of Anillin and Other Mitotic Proteins Are Decreased in DNA-Dependent Protein Kinase Catalytic Subunit-Deficient Cells and Rescued by Inhibition of the Anaphase-Promoting Complex/Cyclosome with proTAME but Not Apcin.Molecular and cellular biology · 2020Article
- Preserving genome integrity in human cells via DNA double-strand break repair.Molecular biology of the cell · 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
4 authors at 1 institution in 1 country.
Funding
Abstract
The binding of DNA-dependent protein kinase catalytic subunit (DNA-PKcs, also known as PRKDC) to Ku proteins at DNA double-strand breaks (DSBs) has long been considered essential for non-homologous end joining (NHEJ) repair, providing a rationale for use of DNA-PKcs inhibitors as cancer therapeutics. Given lagging clinical translation, we reexamined mechanisms and observed instead that DSB repair can proceed independently of DNA-PKcs. While repair of radiation-induced DSBs was blocked in cells expressing shRNAs targeting Ku proteins or other NHEJ core factors, DSBs were repaired on schedule despite targeting DNA-PKcs. Although we failed to observe a DSB repair defect, the γH2AX foci that formed at sites of DNA damage persisted indefinitely after irradiation, leading to cytokinesis failure and accumulation of binucleated cells. Following this mitotic slippage, cells with decreased DNA-PKcs underwent accelerated cellular senescence. We identified downregulation of ataxia-telangiectasia mutated kinase (ATM) as the critical role of DNA-PKcs in recovery from DNA damage, insofar as targeting ATM restored γH2AX foci resolution and cytokinesis. Considering the lack of direct impact on DSB repair and emerging links between senescence and resistance to cancer therapy, these results suggest reassessing DNA-PKcs as a target for cancer treatment.
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.