YTHDC1 m⁶A-dependent and m⁶A-independent functions converge to preserve the DNA damage response.

ABSTRACT: Cells have evolved a robust and highly regulated DNA damage response to preserve their genomic integrity. Although increasing evidence highlights the relevance of RNA regulation, our understanding of its impact on a fully efficient DNA damage response remains limited. Here, through a targeted CRISPR-knockout screen, we identify RNA-binding proteins and modifiers that participate in the p53 response. Among the top hits, we find the m⁶A reader YTHDC1 as a master regulator of p53 expression. YTHDC1 binds to the transcription start sites of TP53 and other genes involved in the DNA damage response, promoting their transcriptional elongation. YTHDC1 deficiency also causes the retention of introns and therefore aberrant protein production of key DNA damage factors. While YTHDC1-mediate

SUBMITTER: Elvira-Blazquez D 

PROVIDER: S-EPMC11329685 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature