N⁶-Methyladenosine, DNA Repair, and Genome Stability

N⁶-methyladenosine (m⁶A) modification in mRNAs and non-coding RNAs is a newly identified epitranscriptomic mark. It provides a fine-tuning of gene expression to serve as a cellular response to endogenous and exogenous stimuli. m⁶A is involved in regulating genes in multiple cellular pathways and functions, including circadian rhythm, cell renewal, differentiation, neurogenesis, immunity, among others. Disruption of m⁶A regulation is associated with cancer, obesity, and immune diseases. Recent studies have shown that m⁶A can be induced by oxidative stress and DNA damage to regulate DNA repair. Also, deficiency of the m⁶A eraser, fat mass obesity-associated protein (FTO) can increase cellular sensitivity to genotoxicants. These findings shed light on the novel roles of m⁶A in modulating DNA repair and genome integrity and stability through responding to DNA damage. In this mini-review, we discuss recent progress in the understanding of a unique role of m⁶As in mRNAs, lncRNAs, and microRNAs in DNA damage response and regulation of DNA repair and genome integrity and instability.