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DNA damage response

Histone H1 deamidation regulates DNA double-strand break repair

Nature Reviews Molecular Cell Biology volume 26, page 418 (2025)Cite this article

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Repair of DNA double-strand breaks (DSBs) requires chromatin opening to permit the access of repair enzymes; however, the mechanisms involved in this process had not been identified. Tian et al. now report in Nature that DSBs prompt CTP synthase 1 (CTPS1; a glutamine amidotransferase) to deamidate two neutral polar asparagine residues, Asn76 and Asn77, in the globular domain of the linker histone H1. This deamidation event, which occurs within a few minutes of DSB formation, is required for the acetylation of H1 Lys75 by the histone acetyltransferase p300. These sequential histone modifications represent a regulatory mechanism that induces chromatin decompaction by reducing the positive charge at the DNA–nucleosome interface. No other mechanisms of chromatin relaxation contribute to this process.

Furthermore, Tian et al. generated acetylation-site-specific antibodies, which confirmed that Lys75 acetylation followed Asn76 and Asn77 deamidation and that Lys75 acetylation levels increased with DNA damage. The researchers then generated HeLa cells with either inducible CTPS1 degradation or an amidotransferase-inactivated CTPS1, which confirmed that the amidotransferase activity of CTPS1 was required and sufficient for DSB repair. This finding was supported by the researchers’ protein structure, which predicted an interaction between the enzymatic cleft of CTPS1 and the Asn76 and Asn77 deamidation sites.

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  1. Nature Reviews Molecular Cell Biology http://www.nature.com/nrm/

    Caroline Barranco

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  1. Caroline Barranco
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Correspondence to Caroline Barranco.

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Barranco, C. Histone H1 deamidation regulates DNA double-strand break repair. Nat Rev Mol Cell Biol 26, 418 (2025). https://doi.org/10.1038/s41580-025-00860-1

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