FIGURE 1.

m⁶A regulates DNA repair to maintain genome stability via R-loops. DNA damage agents induce strand breaks to activate DNA damage response and ATM, which phosphorylates and activates METTL3. DNA damage response then leads to gene transcription and production of m⁶A by activated METTL3 on mRNA transcripts. Subsequently, m⁶A-coated mRNAs hybrid with their DNA template to form R-loops. m⁶A readers such as YTHDF2 and YTHDC1 then bind to m⁶A on R-loops to facilitate DNA repair and resolution of R-loops through RNase H1, thereby leading to genome maintenance.