Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.4.2.30 (
PARP
)
13,611
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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 m
5
C at sites of DNA damage. The RNA methyltransferase
TRDMT1
is recruited to DNA damage sites to promote m
5
C 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 m
5
C-modified RNA. Loss of
TRDMT1
in cancer cells confers sensitivity to
PARP
inhibitors in vitro and in vivo. These results reveal an unexpected
TRDMT1
-m
5
C axis that promotes HR, suggesting that post-transcriptional modifications of RNA can also serve as DNA damage codes to regulate DNA repair.
...
PMID:m
5
C modification of mRNA serves a DNA damage code to promote homologous recombination. 3250 81
