RNA m⁶A regulates DNA repair

Xiang et al. screened human cell lines for chromatin-associated factors that participate in the DNA damage response. Ultraviolet (UV) irradiation caused rapid and transient methylation at the 6 position of adenosine (m⁶A), predominantly in 5′ untranslated regions of poly(A)⁺ RNA, including in transcripts localized at sites of DNA damage. RNA methylation was carried out by the methyltransferase METTL3 together with its cofactor METTL14, and was subsequently removed by the demethylase FTO; methylation was also dependent on PARP, which possibly recruits METTL3 to damage sites. Accumulation of m⁶A following UV irradiation was required for transcription re-initiation and for cell survival, through the recruitment of the repair and translesion synthesis DNA polymerase Pol κ to damage sites. Importantly, METTL3-depleted cells exhibited repair defects, which were rescued by Pol κ overexpression. Together, PARP, METTL3, m⁶A RNA and Pol κ might constitute a new, UV-induced DNA damage repair pathway.