Histone H3 serine-57 is a CHK1 substrate whose phosphorylation affects DNA repair - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue (Data Paper) Nature Communications Année : 2023

Histone H3 serine-57 is a CHK1 substrate whose phosphorylation affects DNA repair

Muhammad Jbara
Marie-Noëlle Prioleau
Ashraf Brik

Résumé

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.
Fichier principal
Vignette du fichier
published version.pdf (10.24 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-04189330 , version 1 (28-08-2023)

Identifiants

Citer

Nikolaos Parisis, Pablo Dans, Muhammad Jbara, Balveer Singh, Diane Schausi-Tiffoche, et al.. Histone H3 serine-57 is a CHK1 substrate whose phosphorylation affects DNA repair. Nature Communications, 2023, 14 (1), pp.5104. ⟨10.1038/s41467-023-40843-4⟩. ⟨hal-04189330⟩
60 Consultations
11 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More