Breaking the script: transcriptional addiction as a driver of genome instability in cancer
Transcription is not only an essential cellular process but also a major source of endogenous DNA strand breaks. Many cancers exhibit transcriptional addiction and rely on dysregulated and excessive transcription to maintain the malignant state. We review recent advances in transcription-associated...
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| Autores principales: | , , |
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| Formato: | Article (Journal) |
| Lenguaje: | inglés |
| Publicado: |
20 November 2025
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| In: |
Trends in genetics
Year: 2026, Volumen: 42, Número: 2, Pages: 177-191 |
| ISSN: | 1362-4555 |
| DOI: | 10.1016/j.tig.2025.10.007 |
| Acceso en línea: | Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.tig.2025.10.007 Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0168952525002616 
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| Notas de Autor: | Osama Hidmi, Pei-Chi Wei, and Rami I. Aqeilan |
| Sumario: | Transcription is not only an essential cellular process but also a major source of endogenous DNA strand breaks. Many cancers exhibit transcriptional addiction and rely on dysregulated and excessive transcription to maintain the malignant state. We review recent advances in transcription-associated DNA breaks and their role as an essential player in endogenous fragility. We highlight the contrast between replication-dependent transcriptional breaks (e.g., transcription-replication conflicts) and replication-independent transcriptional breaks (resulting from transcription itself). We outline two types of transcriptional double-strand breaks (DSBs): promoter-associated breaks that are linked to gene activation, and gene-body breaks that occur stochastically from transcription byproducts. We discuss how supercoiling, R-loops, and enhancer-promoter looping at super-enhancer (SE)-regulated loci can increase DNA fragility and thereby create a distinct Achilles’ heel, and propose that targeting the coupling between SE-driven transcription and DNA repair could offer new therapeutic strategies for cancer. |
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| Notas: | Gesehen am 26.05.2026 |
| Descripción Física: | Online Resource |
| ISSN: | 1362-4555 |
| DOI: | 10.1016/j.tig.2025.10.007 |