Fig. 3: DNA damage response and repair by N6-methyladenosine (m6A).
From: Biological roles of the RNA m6A modification and its implications in cancer
DNA damage response and repair. a Upon genotoxic stress, ATM phosphorylates METTL3, which binds to a DNA lesion, and m6A-modified RNAs direct PARP1 and Pol K for nucleotide excision repair (NER). b The m6A-modified RNAs are recognized by YTHDC1 or YTHDF2, which recruits RAD51 to the damaged region for homologous recombination repair (HRR). c. Reactive oxygen species (ROS) activate the ERK-JNK pathway, which phosphorylates ALKBH5. UBC9 binds to phosphorylated ALKBH5, inducing its SUMOylation. Inhibition of the demethylase activity of ALKBH5 by SUMOylation increases the level of m6A-modified RNAs that are related to DNA damage repair. Transcriptional regulation of DNA damage response and repair. d METTL3 stabilizes the p53 protein in a m6A-independent manner. METTL3 deposits an m6A mark on p53 target mRNAs for regulating the DNA damage response and tumor suppression. This image was created with BioRender (https://biorender.com/).
