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DNA Damage Response

RNA m6A regulates DNA repair

Nature Reviews Molecular Cell Biology volume 18, page 277 (2017)Cite this article

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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.

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References

  1. Xiang, Y. et al. RNA m6A methylation regulates the ultraviolet-induced DNA damage response. Nature http://dx.doi.org/10.1038/nature21671 543, 573–576 (2017)

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  1. Eytan Zlotorynski
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Zlotorynski, E. RNA m6A regulates DNA repair. Nat Rev Mol Cell Biol 18, 277 (2017). https://doi.org/10.1038/nrm.2017.40

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