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m5C modification of mRNA serves a DNA damage code to promote homologous recombination.

Publication ,  Journal Article
Chen, H; Yang, H; Zhu, X; Yadav, T; Ouyang, J; Truesdell, SS; Tan, J; Wang, Y; Duan, M; Wei, L; Zou, L; Levine, AS; Vasudevan, S; Lan, L
Published in: Nat Commun
June 5, 2020

Recruitment of DNA repair proteins to DNA damage sites is a critical step for DNA repair. Post-translational modifications of proteins at DNA damage sites serve as DNA damage codes to recruit specific DNA repair factors. Here, we show that mRNA is locally modified by m5C at sites of DNA damage. The RNA methyltransferase TRDMT1 is recruited to DNA damage sites to promote m5C induction. Loss of TRDMT1 compromises homologous recombination (HR) and increases cellular sensitivity to DNA double-strand breaks (DSBs). In the absence of TRDMT1, RAD51 and RAD52 fail to localize to sites of reactive oxygen species (ROS)-induced DNA damage. In vitro, RAD52 displays an increased affinity for DNA:RNA hybrids containing m5C-modified RNA. Loss of TRDMT1 in cancer cells confers sensitivity to PARP inhibitors in vitro and in vivo. These results reveal an unexpected TRDMT1-m5C axis that promotes HR, suggesting that post-transcriptional modifications of RNA can also serve as DNA damage codes to regulate DNA repair.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

June 5, 2020

Volume

11

Issue

1

Start / End Page

2834

Location

England

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Rad52 DNA Repair and Recombination Protein
  • Rad51 Recombinase
  • RNA, Small Interfering
  • RNA, Messenger
  • RNA Processing, Post-Transcriptional
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Neoplasms
  • Mice
  • Methylation
 

Citation

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ICMJE
MLA
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Chen, H., Yang, H., Zhu, X., Yadav, T., Ouyang, J., Truesdell, S. S., … Lan, L. (2020). m5C modification of mRNA serves a DNA damage code to promote homologous recombination. Nat Commun, 11(1), 2834. https://doi.org/10.1038/s41467-020-16722-7
Chen, Hao, Haibo Yang, Xiaolan Zhu, Tribhuwan Yadav, Jian Ouyang, Samuel S. Truesdell, Jun Tan, et al. “m5C modification of mRNA serves a DNA damage code to promote homologous recombination.Nat Commun 11, no. 1 (June 5, 2020): 2834. https://doi.org/10.1038/s41467-020-16722-7.
Chen H, Yang H, Zhu X, Yadav T, Ouyang J, Truesdell SS, et al. m5C modification of mRNA serves a DNA damage code to promote homologous recombination. Nat Commun. 2020 Jun 5;11(1):2834.
Chen, Hao, et al. “m5C modification of mRNA serves a DNA damage code to promote homologous recombination.Nat Commun, vol. 11, no. 1, June 2020, p. 2834. Pubmed, doi:10.1038/s41467-020-16722-7.
Chen H, Yang H, Zhu X, Yadav T, Ouyang J, Truesdell SS, Tan J, Wang Y, Duan M, Wei L, Zou L, Levine AS, Vasudevan S, Lan L. m5C modification of mRNA serves a DNA damage code to promote homologous recombination. Nat Commun. 2020 Jun 5;11(1):2834.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

June 5, 2020

Volume

11

Issue

1

Start / End Page

2834

Location

England

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Rad52 DNA Repair and Recombination Protein
  • Rad51 Recombinase
  • RNA, Small Interfering
  • RNA, Messenger
  • RNA Processing, Post-Transcriptional
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Neoplasms
  • Mice
  • Methylation