DNA damage-induced YTHDC1 O-GlcNAcylation promotes homologous recombination by enhancing m⁶A binding.

ABSTRACT: N6-methyladenosine (m⁶A) is the most prevalent internal RNA modification, and its regulators include writers, readers and erasers. m⁶A is under stringent control and takes part in many biological events, but it is not known whether there is an interplay between m⁶A and glycosylation. Here we investigated an m⁶A reader, YTHDC1, which has been shown to be recruited to the DNA-RNA hybrid at DNA damage sites and regulate homologous recombination (HR) during DNA damage repair. We found that YTHDC1 is subject to O-linked β-N-acetylglucosamine (O-GlcNAc) modification at Ser396 upon DNA damage, which is pivotal for YTHDC1 chromatin binding and ionization radiation induced focus (IRIF) formation. RNA immunoprecipitation (RIP) and molecular dynamics (MD) s

SUBMITTER: Li M 

PROVIDER: S-EPMC11997583 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature