N6-methyladenosine regulates ATM expression and downstream signaling

N6-methyladenosine (m6A) is the most abundant modification in eukaryotic mRNAs, which plays an important role in regulating multiple biological processes. ATM is a major protein kinase that regulates the DNA damage response. Here, we identified that ATM is a m6A-modificated gene. METTL3 (a m6A writer) and FTO (a m6A eraser) oppositely regulated ATM expression and its downstream signaling. Mechanically, m6A readers YTHDFs and eIF3A suppressed ATM expression in the post-transcriptional levels. We also revealed the oncogenic potential of METTL3 and YTHDF1 related to ATM modulation. This is the first report that ATM, a master in the DNA damage response, is modified by m6A epigenetic modification, and METTL3 disrupts the ATM stability via m6A modification, thereby affecting the DNA-damage response.

Automated summary

m6A modification plays a crucial role in regulating biological processes, including the DNA damage response. METTL3 and YTHDFs control ATM expression through m6A modification, affecting the DNA damage response.