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ID3 deficiency alters chromatin accessibility at DSB sites and enhances vulnerability to HDAC inhibition

The inhibitor of DNA-binding 3 (ID3) plays a crucial role in DNA double-strand break (DSB) repair. We previously reported that ID3 loss reduced chromatin accessibility at DNA repair gene promoters, yet its exact role in DNA repair via chromatin regulation remains elusive. Using the AID-DIvA cell sys...

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Autores principales: Della Corte, Giuditta (Autor) , Eldesouky, Hossam (Autor) , Puchan, Julia (Autor) , Öz, Sercan (Autor) , Everatt, Elena (Autor) , Goyal, Ashish (Autor) , Sigismondo, Gianluca (Autor) , Oppermann, Udo (Autor) , Plass, Christoph (Autor) , Weichenhan, Dieter (Autor) , Bakr, Ali (Autor)
Formato: Article (Journal)
Lenguaje:inglés
Publicado: 24 February 2026
In: International journal of cancer
Year: 2026, Volumen: 158, Número: 12, Pages: 3173-3186
ISSN:1097-0215
DOI:10.1002/ijc.70400
Acceso en línea:Verlag, kostenfrei, Volltext: https://doi.org/10.1002/ijc.70400
Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.70400
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Notas de Autor:Giuditta Della Corte, Hossam Eldesouky, Julia Puchan, Sercan Öz, Elena Everatt, Ashish Goyal, Gianluca Sigismondo, Udo Oppermann, Christoph Plass, Dieter Weichenhan, Ali Bakr
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Sumario:The inhibitor of DNA-binding 3 (ID3) plays a crucial role in DNA double-strand break (DSB) repair. We previously reported that ID3 loss reduced chromatin accessibility at DNA repair gene promoters, yet its exact role in DNA repair via chromatin regulation remains elusive. Using the AID-DIvA cell system with inducible DSBs, we show that ID3 directly regulates chromatin accessibility at DSB sites, as demonstrated by reduced chromatin accessibility and lower H3K27ac levels in ID3-knockout (KO) cells. Loss of ID3 renders cells susceptible to histone deacetylase (HDAC) inhibition, particularly to the Class I HDAC inhibitor, leading to the accumulation of unrepaired DSBs and delayed cell cycle progression. Transcriptome and proteome analyses revealed that HDAC inhibition in ID3-KO cells results in the downregulation of gene sets involved in the regulation of cell cycle and cell division. The synthetic lethality observed between ID3 loss and Class I HDAC inhibition underscores a novel therapeutic vulnerability in ID3-deficient cancers, driven by compounded defects in chromatin remodeling, cell cycle, and DNA repair. Our study provides new insights into the relationship between chromatin regulation and genome stability, with implications for targeted cancer therapies.
Notas:Gesehen am 24.03.2026
Descripción Física:Online Resource
ISSN:1097-0215
DOI:10.1002/ijc.70400

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