H4S47 O-GlcNAcylation regulates the activation of mammalian replication origins.
Nat Struct Mol Biol
; 30(6): 800-811, 2023 06.
Article
em En
| MEDLINE
| ID: mdl-37202474
The transmission and maintenance of genetic information in eukaryotic cells relies on the faithful duplication of the entire genome. In each round of division, excessive replication origins are licensed, with only a fraction activated to give rise to bi-directional replication forks in the context of chromatin. However, it remains elusive how eukaryotic replication origins are selectively activated. Here we demonstrate that O-GlcNAc transferase (OGT) enhances replication initiation by catalyzing H4S47 O-GlcNAcylation. Mutation of H4S47 impairs DBF4-dependent protein kinase (DDK) recruitment on chromatin, causing reduced phosphorylation of the replicative helicase mini-chromosome maintenance (MCM) complex and compromised DNA unwinding. Our short nascent-strand sequencing results further confirm the importance of H4S47 O-GlcNAcylation in origin activation. We propose that H4S47 O-GlcNAcylation directs origin activation through facilitating MCM phosphorylation, and this may shed light on the control of replication efficiency by chromatin environment.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ciclo Celular
/
Proteínas de Saccharomyces cerevisiae
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article