TY - JOUR
T1 - Histone H3 serine-57 is a CHK1 substrate whose phosphorylation affects DNA repair
AU - Parisis, Nikolaos
AU - Dans, Pablo D.
AU - Jbara, Muhammad
AU - Singh, Balveer
AU - Schausi-Tiffoche, Diane
AU - Molina-Serrano, Diego
AU - Brun-Heath, Isabelle
AU - Hendrychová, Denisa
AU - Maity, Suman Kumar
AU - Buitrago, Diana
AU - Lema, Rafael
AU - Nait Achour, Thiziri
AU - Giunta, Simona
AU - Girardot, Michael
AU - Talarek, Nicolas
AU - Rofidal, Valérie
AU - Danezi, Katerina
AU - Coudreuse, Damien
AU - Prioleau, Marie Noëlle
AU - Feil, Robert
AU - Orozco, Modesto
AU - Brik, Ashraf
AU - Wu, Pei Yun Jenny
AU - Krasinska, Liliana
AU - Fisher, Daniel
N1 - Publisher Copyright:
© 2023, Springer Nature Limited.
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85168672936&partnerID=8YFLogxK
U2 - 10.1038/s41467-023-40843-4
DO - 10.1038/s41467-023-40843-4
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C2 - 37607906
AN - SCOPUS:85168672936
SN - 2041-1723
VL - 14
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5104
ER -
