ArticleFEBS open bio2019
Genotoxic stress causes the accumulation of DNA-dependent protein kinase catalytic subunit phosphorylated at serine 2056 at nuclear speckles and alters pre-mRNA alternative splicing.
Article in FEBS open bio, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 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
9 citing papers in PubMed, 9 citations in OpenAlex.
- Targeting DNA-PK: medicinal chemistry insights into small-molecule inhibitor discovery and optimisation.RSC medicinal chemistry · 2026Review
- Huntingtin (HTT) interactome in regulation of DNA repair/remodeling and RNA processing pathways.Life science alliance · 2026Article
- DNA-PKcs, a player winding and dancing with RNA metabolism and diseases.Cellular & molecular biology letters · 2025Review
- Disruption of RNA Splicing Increases Vulnerability of Cells to DNA-PK Inhibitors.International journal of molecular sciences · 2024Article
- DNA Damage Regulates the Functions of the RNA Binding Protein Sam68 through ATM-Dependent Phosphorylation.Cancers · 2022Article
- DNA-PKcs restrictsFrontiers in immunology · 2022Article
- Coordination of RNA Processing Regulation by Signal Transduction Pathways.Biomolecules · 2021Review
- Review
- Reciprocal regulation between alternative splicing and the DNA damage response.Genetics and molecular biology · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RNA splicing has emerged as a critical player in the DNA damage response (DDR). However, the underlying mechanism(s) by which pre-mRNA splicing is coordinately regulated by genotoxic stress has remained largely unclear. Here, we show that a DDR factor, DNA-dependent protein kinase (DNA-PK), participates in the modulation of pre-mRNA splicing in the presence of DNA double-strand break (DSB)-induced genotoxic stress. Through indirect immunostaining, we made the surprising discovery that DNA-PK catalytic subunits (DNA-PKcs) autophosphorylated at serine 2056 (S2056) accumulate at nuclear speckles (dynamic nuclear structures that are enriched with splicing factors), following their dissociation from DSB lesions. Inactivation of DNA-PKcs, either using a small molecule inhibitor or by RNA interference, alters alternative splicing of a set of pre-mRNAs in A549 cells treated with the topoisomerase II inhibitor mitoxantrone, indicative of an involvement of DNA-PKcs in modulating pre-mRNA splicing following genotoxic stress. These findings indicate a novel physical and functional connection between the DNA damage response and pre-mRNA splicing, and enhance our understanding of how mRNA splicing is involved in the cellular response to DSB lesions.
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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.