ArticleMolecular cell2022
Calcineurin dephosphorylates topoisomerase IIβ and regulates the formation of neuronal-activity-induced DNA breaks.
Article in Molecular cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 45 citations in OpenAlex.
- RNAPII and DNA supercoiling regulate cohesin engagement in neurons.Nucleic acids research · 2026Article
- Article
- DNA topological regulation in RNA polymerase II transcription.Cellular & molecular biology letters · 2026Review
- The Roles of Topoisomerases in Transcriptional Regulation.International journal of molecular sciences · 2026Review
- Topoisomerase IIα orchestrates secretion of IL-6 and IL-8 with human papillomavirus replication.Virologica Sinica · 2025Article
- Stra8 links neuronal activity to inhibitory circuit protection in the adult mouse brain.Cell reports · 2025Article
- Toxoplasma gondii infection and chronic IL-1 elevation drive hippocampal DNA double-strand break signaling, leading to cognitive deficits.Nature neuroscience · 2025Article
- RNA transcripts serve as a template for double-strand break repair in human cells.Nature communications · 2025Article
- Review
- How do neurons live long and healthy? The mechanism of neuronal genome integrity.Frontiers in neuroscience · 2025Review
- Infantile epileptic spasms syndrome as a new phenotype in TOP2B deficiency caused by aFrontiers in pediatrics · 2025Article
- A long noncoding eRNA forms R-loops to shape emotional experience-induced behavioral adaptation.Science (New York, N.Y.) · 2024Article
- Structural insights into the assembly of type IIA topoisomerase DNA cleavage-religation center.Nucleic acids research · 2024Article
- Tau beyond Tangles: DNA Damage Response and Cytoskeletal Protein Crosstalk on Neurodegeneration.International journal of molecular sciences · 2024Review
- R-loop resolution by ARIP4 helicase promotes androgen-mediated transcription induction.Science advances · 2024Article
- Adaptive and Maladaptive DNA Breaks in Neuronal Physiology and Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Mapping catalytically engaged TOP2B in neurons reveals the principles of topoisomerase action within the genome.Cell reports · 2024Article
- A cyclin D1 intrinsically disordered domain accesses modified histone motifs to govern gene transcription.Oncogenesis · 2024Article
- Evidence that Alzheimer's Disease Is a Disease of Competitive Synaptic Plasticity Gone Awry.Journal of Alzheimer's disease : JAD · 2024Review
- Loss of Adaptive DNA Breaks in Alzheimer's Disease Brains.Journal of Alzheimer's disease : JAD · 2024Article
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Neuronal activity induces topoisomerase IIβ (Top2B) to generate DNA double-strand breaks (DSBs) within the promoters of neuronal early response genes (ERGs) and facilitate their transcription, and yet, the mechanisms that control Top2B-mediated DSB formation are unknown. Here, we report that stimulus-dependent calcium influx through NMDA receptors activates the phosphatase calcineurin to dephosphorylate Top2B at residues S1509 and S1511, which stimulates its DNA cleavage activity and induces it to form DSBs. Exposing mice to a fear conditioning paradigm also triggers Top2B dephosphorylation at S1509 and S1511 in the hippocampus, indicating that calcineurin also regulates Top2B-mediated DSB formation following physiological neuronal activity. Furthermore, calcineurin-Top2B interactions following neuronal activity and sites that incur activity-induced DSBs are preferentially localized at the nuclear periphery in neurons. Together, these results reveal how radial gene positioning and the compartmentalization of activity-dependent signaling govern the position and timing of activity-induced DSBs and regulate gene expression patterns in neurons.
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