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

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

Nature communications (2020-06-07)
Hao Chen, Haibo Yang, Xiaolan Zhu, Tribhuwan Yadav, Jian Ouyang, Samuel S Truesdell, Jun Tan, Yumin Wang, Meihan Duan, Leizhen Wei, Lee Zou, Arthur S Levine, Shobha Vasudevan, Li Lan
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
MISSION® esiRNA, targeting human TRDMT1 (1)
Sigma-Aldrich
Methylene blue, certified by the Biological Stain Commission
Sigma-Aldrich
Ponceau S, BioReagent, suitable for electrophoresis
Sigma-Aldrich
Bovine Serum Albumin, heat shock fraction, protease free, fatty acid free, essentially globulin free, pH 7, ≥98%