The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
RNA m6A methylation regulates the ultraviolet-induced DNA damage response
Open accessAbstract
Cell proliferation and survival require the faithful maintenance and propagation of genetic information, which are threatened by the ubiquitous sources of DNA damage present intracellularly and in the external environment. A system of DNA repair, called the DNA damage response, detects and repairs damaged DNA and prevents cell division until the repair is complete. Here we report that methylation at the 6 position of adenosine (m6A) in RNA is rapidly (within 2 min) and transiently induced at DNA damage sites in response to ultraviolet irradiation. This modification occurs on numerous poly(A)+ transcripts and is regulated by the methyltransferase METTL3 (methyltransferase-like 3) and the demethylase FTO (fat mass and obesity-associated protein). In the absence of METTL3 catalytic activity, cells showed delayed repair of ultraviolet-induced cyclobutane pyrimidine adducts and elevated sensitivity to ultraviolet, demonstrating the importance of m6A in the ultraviolet-responsive DNA damage response. Multiple DNA polymerases are involved in the ultraviolet response, some of which resynthesize DNA after the lesion has been excised by the nucleotide excision repair pathway, while others participate in trans-lesion synthesis to allow replication past damaged lesions in S phase. DNA polymerase κ (Pol κ), which has been implicated in both nucleotide excision repair and trans-lesion synthesis, required the catalytic activity of METTL3 for immediate localization to ultraviolet-induced DNA damage sites. Importantly, Pol κ overexpression qualitatively suppressed the cyclobutane pyrimidine removal defect associated with METTL3 loss. Thus, we have uncovered a novel function for RNA m6A modification in the ultraviolet-induced DNA damage response, and our findings collectively support a model in which m6A RNA serves as a beacon for the selective, rapid recruitment of Pol κ to damage sites to facilitate repair and cell survival.
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Trapnell, C., Williams, B. A., Pertea, G., Mortazavi, A., Kwan, G., van Baren, M. J., Salzberg, S. L., Wold, B. J., & Pachter, L. (2010) · Nature Biotechnology · doi:10.1038/nbt.1621 · Cited by 15,556
N6-methyladenosine-dependent regulation of messenger RNA stability
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“The reported roles for m 6 A methylation involve regulation of RNA fate--such as stability 11 , translation 12–14 , splicing 15–17 , and miRNA processing 18,19 , and promoting differentiation 20 , pluripotency 21 , X chromosome inactivation 22 , and responses to cellular stresses 12,14,15 .”
Self-citationThe DNA Damage Response: Making It Safe to Play with Knives
Ciccia, A., & Elledge, S. J. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.019 · Cited by 4,368
N6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO
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Self-citationALKBH5 Is a Mammalian RNA Demethylase that Impacts RNA Metabolism and Mouse Fertility
Zheng, G., Dahl, J. A., Niu, Y., Fedorcsak, P., Huang, C.-M., Li, C. J., Vågbø, C. B., Shi, Y., Wang, W.-L., Song, S.-H., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2012.10.015 · Cited by 3,550
Self-citationN6-methyladenosine Modulates Messenger RNA Translation Efficiency
Wang, X., Zhao, B. S., Roundtree, I. A., Lu, Z., Han, D., Ma, H., Weng, X., Chen, K., Shi, H., & He, C. (2015) · Cell · doi:10.1016/j.cell.2015.05.014 · Cited by 3,483
Self-citationm6A RNA methylation promotes XIST-mediated transcriptional repression
Patil, D. P., Chen, C.-K., Pickering, B. F., Chow, A., Jackson, C., Guttman, M., & Jaffrey, S. R. (2016) · Nature · doi:10.1038/nature19342 · Cited by 1,747
HNRNPA2B1 Is a Mediator of m6A-Dependent Nuclear RNA Processing Events
Alarcón, C. R., Goodarzi, H., Lee, H., Liu, X., Tavazoie, S., & Tavazoie, S. F. (2015) · Cell · doi:10.1016/j.cell.2015.08.011 · Cited by 1,514
Eukaryotic Translesion Polymerases and Their Roles and Regulation in DNA Damage Tolerance
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“Although BrdU was incorporated into cellular DNA before UV irradiation to enhance the DDR, as described 25 , localized m 6 A RNA also occurred in UV-irradiated FTO KO cells lacking BrdU (data not shown), and no m 6 A RNA was detected in γ -irradiated cells containing BrdU (Fig.”
Cited by
The role of m6A modification in the biological functions and diseases
Jiang, X., Liu, B., Nie, Z., Duan, L., Xiong, Q., Jin, Z., Yang, C., & Chen, Y. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00450-x · Cited by 2,335
Histone H3 trimethylation at lysine 36 guides m6A RNA modification co-transcriptionally
Huang, H., Weng, H., Zhou, K., Wu, T., Zhao, B. S., Sun, M., Chen, Z., Deng, X., Xiao, G., Auer, F., et al. (2019) · Nature · doi:10.1038/s41586-019-1016-7 · Cited by 677
Self-citationN6-Methyladenine DNA Modification in the Human Genome
Xiao, C.-L., Zhu, S., He, M., Chen, D., Zhang, Q., Chen, Y., Yu, G., Liu, J., Xie, S.-Q., Luo, F., et al. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.06.015 · Cited by 531
Interactions, localization, and phosphorylation of the m6A generating METTL3–METTL14–WTAP complex
Schöller, E., Weichmann, F., Treiber, T., Ringle, S., Treiber, N., Flatley, A., Feederle, R., Bruckmann, A., & Meister, G. (2018) · RNA · doi:10.1261/rna.064063.117 · Cited by 439
m 6 A in mRNA: An Ancient Mechanism for Fine-Tuning Gene Expression
Roignant, J.-Y., & Soller, M. (2017) · Trends in Genetics · doi:10.1016/j.tig.2017.04.003 · Cited by 426
Metadata
- Authors
- Xiang, Y., Laurent, B., Hsu, C.-H., Nachtergaele, S., Lu, Z., Sheng, W., Xu, C., Chen, H., Ouyang, J., Wang, S., Ling, D., Hsu, P.-H., Zou, L., Jambhekar, A., He, C., & Shi, Y.
- Venue
- Nature
- Published
- 2017-03-15
- Volume
- 543
- Issue
- 7646
- Pages
- 573-576
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2597375791
- Cited by
- 911
- References
- 13
- FWCI
- 28.63
- Type
- journal article
- Language
- en
- Open access
- green
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- Xiang, Y., Laurent, B., Hsu, C.-H., Nachtergaele, S., Lu, Z., Sheng, W., Xu, C., Chen, H., Ouyang, J., Wang, S., Ling, D., Hsu, P.-H., Zou, L., Jambhekar, A., He, C., & Shi, Y. (2017). RNA m6A methylation regulates the ultraviolet-induced DNA damage response. Nature. https://doi.org/10.1038/nature21671
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