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- Title
Histone H3 serine-57 is a CHK1 substrate whose phosphorylation affects DNA repair.
- Authors
Parisis, Nikolaos; Dans, Pablo D.; Jbara, Muhammad; Singh, Balveer; Schausi-Tiffoche, Diane; Molina-Serrano, Diego; Brun-Heath, Isabelle; Hendrychová, Denisa; Maity, Suman Kumar; Buitrago, Diana; Lema, Rafael; Nait Achour, Thiziri; Giunta, Simona; Girardot, Michael; Talarek, Nicolas; Rofidal, Valérie; Danezi, Katerina; Coudreuse, Damien; Prioleau, Marie-Noëlle; Feil, Robert
- Abstract
Histone post-translational modifications promote a chromatin environment that controls transcription, DNA replication and repair, but surprisingly few phosphorylations have been documented. We report the discovery of histone H3 serine-57 phosphorylation (H3S57ph) and show that it is implicated in different DNA repair pathways from fungi to vertebrates. We identified CHK1 as a major human H3S57 kinase, and disrupting or constitutively mimicking H3S57ph had opposing effects on rate of recovery from replication stress, 53BP1 chromatin binding, and dependency on RAD52. In fission yeast, mutation of all H3 alleles to S57A abrogated DNA repair by both non-homologous end-joining and homologous recombination, while cells with phospho-mimicking S57D alleles were partly compromised for both repair pathways, presented aberrant Rad52 foci and were strongly sensitised to replication stress. Mechanistically, H3S57ph loosens DNA-histone contacts, increasing nucleosome mobility, and interacts with H3K56. Our results suggest that dynamic phosphorylation of H3S57 is required for DNA repair and recovery from replication stress, opening avenues for investigating the role of this modification in other DNA-related processes. Histone post-translational modifications control several fundamental processes on DNA. Here, the authors describe a conserved phosphorylation of histone H3 on the globular core and show that it loosens the nucleosome and regulates DNA repair.
- Subjects
DNA repair; CHECKPOINT kinase 1; POST-translational modification; PHOSPHORYLATION; DNA replication
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-40843-4