ArticleNature communications2024
DHX9 SUMOylation is required for the suppression of R-loop-associated genome instability.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- GEF-H1 upon microtubule destabilization drives ZBP1-dependent necroptosis.Cell death and differentiation · 2026Article
- GSLR Drives Lung Adenocarcinoma as a Critical Regulator of Energy Homeostasis Through Creatine Kinase B Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- R-loops in colorectal cancer: mechanisms, mapping strategies, and therapeutic opportunities.Molecular biology reports · 2026Review
- The role of non-coding RNAs in regulating R-loop dynamics in cancer: Mechanisms and therapeutic implications.Acta pharmaceutica Sinica. B · 2026Review
- DHX9 transcriptional upregulation and lactylation at K1024 fuels a glycolysis-histone lactylation loop in osteosarcoma.Journal of translational medicine · 2026Article
- Dual roles of the DHX9 RGG domain in hybrid-dependent recruitment and suppression of 53BP1.Scientific reports · 2026Article
- Protocol for SUMO fusion-based functional rescue of SUMOylation-defective protein in Drosophila.STAR protocols · 2026Article
- DDX5 (p68) and UbE2T as emerging superior cancer therapeutic targets: dual molecular glue target degradation by FL118 for conquering difficult-to-treat cancers.Journal of experimental & clinical cancer research : CR · 2026Review
- Inhibition of PRMT5 triggers synthetic lethality in ARID1A-deficient endometrial cancer by promoting aberrant R-loop accumulation.Molecular cancer · 2026Article
- Regulation of R-Loop Dynamics by Proteins and Long Noncoding RNAs: An Emerging Paradigm for Cancer Treatment.Cancer science · 2026Review
- Dual roles of DEAD-box RNA helicase Brr2 in genome stability regulation.Nature communications · 2025Article
- Co-opted SUMO machinery promotes condensate formation associated with membranous replication organelles of a positive-strand RNA virus.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Challenges and opportunities for the diverse substrates of SPOP E3 ubiquitin ligase in cancer.Theranostics · 2025Review
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Authors and funding
10 authors.
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Abstract
RNA helicase DHX9 is essential for genome stability by resolving aberrant R-loops. However, its regulatory mechanisms remain unclear. Here we show that SUMOylation at lysine 120 (K120) is crucial for DHX9 function. Preventing SUMOylation at K120 leads to R-loop dysregulation, increased DNA damage, and cell death. Cells expressing DHX9 K120R mutant which cannot be SUMOylated are more sensitive to genotoxic agents and this sensitivity is mitigated by RNase H overexpression. Unlike the mutant, wild-type DHX9 interacts with R-loop-associated proteins such as PARP1 and DDX21 via SUMO-interacting motifs. Fusion of SUMO2 to the DHX9 K120R mutant enhances its association with these proteins, reduces R-loop accumulation, and alleviates survival defects of DHX9 K120R. Our findings highlight the critical role of DHX9 SUMOylation in maintaining genome stability by regulating protein interactions necessary for R-loop balance.
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