The DOI matches its Crossref record; 80 of the 80 references it cites were found in a registry or an index.
METTL3 and N6-Methyladenosine Promote Homologous Recombination-Mediated Repair of DSBs by Modulating DNA-RNA Hybrid Accumulation
Open accessAbstract
Double-strand breaks (DSBs) are the most deleterious DNA lesions, which, if left unrepaired, may lead to genome instability or cell death. Here, we report that, in response to DSBs, the RNA methyltransferase METTL3 is activated by ATM-mediated phosphorylation at S43. Phosphorylated METTL3 is then localized to DNA damage sites, where it methylates the N6 position of adenosine (m6A) in DNA damage-associated RNAs, which recruits the m6A reader protein YTHDC1 for protection. In this way, the METTL3-m6A-YTHDC1 axis modulates accumulation of DNA-RNA hybrids at DSBs sites, which then recruit RAD51 and BRCA1 for homologous recombination (HR)-mediated repair. METTL3-deficient cells display defective HR, accumulation of unrepaired DSBs, and genome instability. Accordingly, depletion of METTL3 significantly enhances the sensitivity of cancer cells and murine xenografts to DNA damage-based therapy. These findings uncover the function of METTL3 and YTHDC1 in HR-mediated DSB repair, which may have implications for cancer therapy.
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Cited by
Hidden codes in mRNA: Control of gene expression by m6A
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Metadata
- Authors
- Zhang, C., Chen, L., Peng, D., Jiang, A., He, Y., Zeng, Y., Xie, C., Zhou, H., Luo, X., Liu, H., Chen, L., Ren, J., Wang, W., & Zhao, Y.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2020-08
- Volume
- 79
- Issue
- 3
- Pages
- 425-442.e7
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W3038967150
- Cited by
- 331
- References
- 80
- FWCI
- 11.48
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Zhang, C., Chen, L., Peng, D., Jiang, A., He, Y., Zeng, Y., Xie, C., Zhou, H., Luo, X., Liu, H., Chen, L., Ren, J., Wang, W., & Zhao, Y. (2020). METTL3 and N6-Methyladenosine Promote Homologous Recombination-Mediated Repair of DSBs by Modulating DNA-RNA Hybrid Accumulation. Molecular Cell. https://doi.org/10.1016/j.molcel.2020.06.017
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