ArticleNucleic acids research2016
DNA-PK triggers histone ubiquitination and signaling in response to DNA double-strand breaks produced during the repair of transcription-blocking topoisomerase I lesions.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 48 citations in OpenAlex.
- Persistent TOP1 cleavage complexes in drug-tolerant cells drive adaptive resistance to EGFR-targeted therapies in lung cancer.Science advances · 2026Article
- PARP1 trapping activates ATM-mediated NF-κB signaling independent of replication in response to TOP1 blockade.Nucleic acids research · 2026Article
- Superenhancers shape the landscape and repair dynamics of transcription-associated DNA breaks in cancer.Science advances · 2026Article
- H263A and SCAN1/H493R mutant TDP1 block TOP1-induced double-strand break repair during gene transcription in quiescent cells and promote cell death.Cell death & disease · 2025Article
- The DNA repair protein DNA-PKcs modulates synaptic plasticity via PSD-95 phosphorylation and stability.EMBO reports · 2024Article
- TOP1 and R-loops facilitate transcriptional DSBs at hypertranscribed cancer driver genes.iScience · 2024Article
- TDP1 suppresses chromosomal translocations and cell death induced by abortive TOP1 activity during gene transcription.Nature communications · 2023Article
- MUS81 cleaves TOP1-derived lesions and other DNA-protein cross-links.BMC biology · 2023Article
- SPRTN-dependent DPC degradation precedes repair of damaged DNA: a proof of concept revealed by the STAR assay.Nucleic acids research · 2023Article
- RNase H2, mutated in Aicardi-Goutières syndrome, resolves co-transcriptional R-loops to prevent DNA breaks and inflammation.Nature communications · 2022Article
- eIF3a-PPP2R5A-mediated ATM/ATR dephosphorylation is essential for irinotecan-induced DNA damage response.Cell proliferation · 2022Article
- Defective repair of topoisomerase I induced chromosomal damage in Huntington's disease.Cellular and molecular life sciences : CMLS · 2022Article
- Cellular functions of the protein kinase ATM and their relevance to human disease.Nature reviews. Molecular cell biology · 2021Review
- ATM antagonizes NHEJ proteins assembly and DNA-ends synapsis at single-ended DNA double strand breaks.Nucleic acids research · 2020Article
- PARylation During Transcription: Insights into the Fine-Tuning Mechanism and Regulation.Cancers · 2020Review
- Dual Processing of R-Loops and Topoisomerase I Induces Transcription-Dependent DNA Double-Strand Breaks.Cell reports · 2019Article
- Topological DNA damage, telomere attrition and T cell senescence during chronic viral infections.Immunity & ageing : I & A · 2019Article
- Evaluation of ATM Kinase Inhibitor KU-55933 as Potential Anti-Frontiers in cellular and infection microbiology · 2019Article
- PARP-1-dependent RND1 transcription induced by topoisomerase I cleavage complexes confers cellular resistance to camptothecin.Cell death & disease · 2018Article
- RNA/DNA Hybrid Interactome Identifies DXH9 as a Molecular Player in Transcriptional Termination and R-Loop-Associated DNA Damage.Cell reports · 2018Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although defective repair of DNA double-strand breaks (DSBs) leads to neurodegenerative diseases, the processes underlying their production and signaling in non-replicating cells are largely unknown. Stabilized topoisomerase I cleavage complexes (Top1cc) by natural compounds or common DNA alterations are transcription-blocking lesions whose repair depends primarily on Top1 proteolysis and excision by tyrosyl-DNA phosphodiesterase-1 (TDP1). We previously reported that stabilized Top1cc produce transcription-dependent DSBs that activate ATM in neurons. Here, we use camptothecin (CPT)-treated serum-starved quiescent cells to induce transcription-blocking Top1cc and show that those DSBs are generated during Top1cc repair from Top1 peptide-linked DNA single-strand breaks generated after Top1 proteolysis and before excision by TDP1. Following DSB induction, ATM activates DNA-PK whose inhibition suppresses H2AX and H2A ubiquitination and the later assembly of activated ATM into nuclear foci. Inhibition of DNA-PK also reduces Top1 ubiquitination and proteolysis as well as resumption of RNA synthesis suggesting that DSB signaling further enhances Top1cc repair. Finally, we show that co-transcriptional DSBs kill quiescent cells. Together, these new findings reveal that DSB production and signaling by transcription-blocking Top1 lesions impact on non-replicating cell fate and provide insights on the molecular pathogenesis of neurodegenerative diseases such as SCAN1 and AT syndromes, which are caused by TDP1 and ATM deficiency, respectively.
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