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HDAC1 has a role in double strand break repair by regulating γH2AX signalling

Marqueta-Gracia, J.; Bejarano-Franco, M.; Spaag, S.; Silva, S.; Aguilera, A.; Gomez-Gonzalez, B.

2025-11-18 molecular biology
10.1101/2025.11.18.689006 bioRxiv
Show abstract

Genome integrity is challenged by DNA damage. DNA double-strand breaks are the most harmful DNA lesions as they block DNA replication and transcription leading to chromosome reorganisations or cell death if not properly repaired. In addition, increasing evidence points to chromatin as a relevant modulator of the efficiency of repair in eukaryotes. Here, we show that inhibition or depletion of human histone deacetylase 1 (HDAC1) regulates DSB repair by controlling the phosphorylation of H2AX, an early step of the DNA damage response. Thus, DSB repair is regulated by a crosstalk between histone acetylation and phosphorylation. Our study provides evidence that histone acetylation regulates DSB signalling supporting that histone deacetylase inhibitors could enhance genotoxic treatment of cancer.

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