ArticleNucleic acids research2023
TATDN2 resolution of R-loops is required for survival of BRCA1-mutant cancer cells.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- PCNA-RECQL5-RPRD1B recruit repair components to stressed replication forks to promote survival of BRCA1-deficient cancer cells.Nucleic acids research · 2026Article
- R-loop processing via REXO4-RNaseH1-mediated endo- and exo-cleavage coupling mode prevents genome instability and antitumor immunity.Science advances · 2026Article
- Regulation of R-Loop Dynamics by Proteins and Long Noncoding RNAs: An Emerging Paradigm for Cancer Treatment.Cancer science · 2026Review
- Tatdn2 is required for DNA repair to safeguard genome stability in primordial germ cells.Nucleic acids research · 2025Article
- Tectoridin modulates intertwined molecular pathways in metabolic syndrome: insights from network pharmacology, molecular docking, and in vivo studies.Inflammopharmacology · 2025Article
- CRISPR/Cas9 Screening Highlights PFKFB3 Gene as a Major Contributor to 5-Fluorouracil Resistance in Esophageal Cancer.Cancers · 2025Article
- R-loops and small RNA regulatory interactions: mechanisms and clinical perspectives.Frontiers in cell and developmental biology · 2025Review
- Significance of diagnostic and therapeutic potential of serum endothelial and inflammatory biomarkers in defining disease severity of dengue infected patients.Medical microbiology and immunology · 2024Article
- HPV induced R-loop formation represses innate immune gene expression while activating DNA damage repair pathways.PLoS pathogens · 2024Article
- R-loop and diseases: the cell cycle matters.Molecular cancer · 2024Review
- Cellular Responses to Widespread DNA Replication Stress.International journal of molecular sciences · 2023Review
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
Abstract
BRCA1-deficient cells have increased IRE1 RNase, which degrades multiple microRNAs. Reconstituting expression of one of these, miR-4638-5p, resulted in synthetic lethality in BRCA1-deficient cancer cells. We found that miR-4638-5p represses expression of TATDN2, a poorly characterized member of the TATD nuclease family. We discovered that human TATDN2 has RNA 3' exonuclease and endonuclease activity on double-stranded hairpin RNA structures. Given the cleavage of hairpin RNA by TATDN2, and that BRCA1-deficient cells have difficulty resolving R-loops, we tested whether TATDN2 could resolve R-loops. Using in vitro biochemical reconstitution assays, we found TATDN2 bound to R-loops and degraded the RNA strand but not DNA of multiple forms of R-loops in vitro in a Mg2+-dependent manner. Mutations in amino acids E593 and E705 predicted by Alphafold-2 to chelate an essential Mg2+ cation completely abrogated this R-loop resolution activity. Depleting TATDN2 increased cellular R-loops, DNA damage and chromosomal instability. Loss of TATDN2 resulted in poor replication fork progression in the presence of increased R-loops. Significantly, we found that TATDN2 is essential for survival of BRCA1-deficient cancer cells, but much less so for cognate BRCA1-repleted cancer cells. Thus, we propose that TATDN2 is a novel target for therapy of BRCA1-deficient cancers.
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Registered trials
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