ArticleThe EMBO journal2022
Loss of ribonuclease DIS3 hampers genome integrity in myeloma by disrupting DNA:RNA hybrid metabolism.
Article in The EMBO journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Review
- HELZ is a RNA-DNA helicase that resolves R loops to facilitate homologous recombination repair.Nature communications · 2026Article
- Ribonuclease DIS3 delays aging and senescence by generating tRNA halves.Nature communications · 2026Article
- ADAR1 and ADAR2 associate with the RNA exosome and modulate RNA stability.Nucleic acids research · 2026Article
- DIS3 mutations enhance AID-driven translocations during B-cell activation, promoting transformation to multiple myeloma.Nature communications · 2026Article
- DIS3 licenses B cells for plasma cell differentiation in humans.Cellular & molecular immunology · 2026Article
- JAK2V617FMolecular therapy. Nucleic acids · 2025Article
- Atypical R-loops in cancer: decoding molecular chaos for therapeutic gain.Journal of translational medicine · 2025Review
- Cellular imbalance of specific RNA-binding proteins associates with harmful R-loops.PLoS genetics · 2025Article
- Transcriptional repression facilitates RNA:DNA hybrid accumulation at DNA double-strand breaks.Nature cell biology · 2025Article
- RNA biogenesis and RNA metabolism factors as R-loop suppressors: a hidden role in genome integrity.Genes & development · 2024Review
- Multiple myeloma-associatedBlood neoplasia · 2024Article
- RNA processing mechanisms contribute to genome organization and stability in B cells.Oncogene · 2024Review
- Article
- Break-induced RNA-DNA hybrids (BIRDHs) in homologous recombination: friend or foe?EMBO reports · 2023Review
- RAD51 Inhibition Shows Antitumor Activity in Hepatocellular Carcinoma.International journal of molecular sciences · 2023Article
- Review
- Loss of ribonuclease DIS3 hampers genome integrity in myeloma by disrupting DNA:RNA hybrid metabolism.The EMBO journal · 2022Article
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ribonuclease DIS3 is one of the most frequently mutated genes in the hematological cancer multiple myeloma, yet the basis of its tumor suppressor function in this disease remains unclear. Herein, exploiting the TCGA dataset, we found that DIS3 plays a prominent role in the DNA damage response. DIS3 inactivation causes genomic instability by increasing mutational load, and a pervasive accumulation of DNA:RNA hybrids that induces genomic DNA double-strand breaks (DSBs). DNA:RNA hybrid accumulation also prevents binding of the homologous recombination (HR) machinery to double-strand breaks, hampering DSB repair. DIS3-inactivated cells become sensitive to PARP inhibitors, suggestive of a defect in homologous recombination repair. Accordingly, multiple myeloma patient cells mutated for DIS3 harbor an increased mutational burden and a pervasive overexpression of pro-inflammatory interferon, correlating with the accumulation of DNA:RNA hybrids. We propose DIS3 loss in myeloma to be a driving force for tumorigenesis via DNA:RNA hybrid-dependent enhanced genome instability and increased mutational rate. At the same time, DIS3 loss represents a liability that might be therapeutically exploited in patients whose cancer cells harbor DIS3 mutations.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.