ArticleNucleic acids research2024
ATR phosphorylates DHX9 at serine 321 to suppress R-loop accumulation upon genotoxic stress.
Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 31 citations in OpenAlex.
- GSLR Drives Lung Adenocarcinoma as a Critical Regulator of Energy Homeostasis Through Creatine Kinase B Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- DHX9 Inhibition Enhances Paclitaxel Sensitivity by Inducing Mitotic Failure in Ovarian and Endometrial Cancers.Molecular cancer therapeutics · 2026Article
- R-loops in colorectal cancer: mechanisms, mapping strategies, and therapeutic opportunities.Molecular biology reports · 2026Review
- Dual roles of the DHX9 RGG domain in hybrid-dependent recruitment and suppression of 53BP1.Scientific reports · 2026Article
- An overview of the DNA damage response in female reproductive system and breast cancers: A narrative review.International journal of reproductive biomedicine · 2026Review
- DHX9 sustains hematopoietic stem cell function in cooperation with H3 acetylation.Stem cell reports · 2026Article
- Inhibition of PRMT5 triggers synthetic lethality in ARID1A-deficient endometrial cancer by promoting aberrant R-loop accumulation.Molecular cancer · 2026Article
- Article
- Crosstalk Between R-Loops, RNA/DNA Modifications, and Cell Death Dynamics in Canine Models of Retinitis Pigmentosa.Investigative ophthalmology & visual science · 2026Article
- Regulation of R-Loop Dynamics by Proteins and Long Noncoding RNAs: An Emerging Paradigm for Cancer Treatment.Cancer science · 2026Review
- Targeting R-loops: diverse RNA helicases in R-loop resolution and their potential as targets for cancer therapy.Frontiers in cell and developmental biology · 2026Review
- Inducing tumor-intrinsic innate immune response to break cancer immunotherapy resistance.Frontiers in medicine · 2026Review
- Comprehensive identification of proteins interacting with long non-coding RNA TUG1 in R-loop regulation.Journal of biochemistry · 2025Article
- DNA damage response and cell fate decisions across the lifespan: from fetal development to age-related respiratory diseases.Cell & bioscience · 2025Review
- Participants in Transcription-Replication Conflict and Their Role in Formation and Resolution of R-Loops.International journal of molecular sciences · 2025Review
- Off-pore Nup98 condensates mobilize heterochromatic breaks and exclude Rad51.Molecular cell · 2025Article
- KLF5 loss sensitizes cells to ATR inhibition and is synthetic lethal with ARID1A deficiency.Nature communications · 2025Article
- R-loops and small RNA regulatory interactions: mechanisms and clinical perspectives.Frontiers in cell and developmental biology · 2025Review
- Mechanisms underlining R-loop biology and implications for human disease.Frontiers in cell and developmental biology · 2025Review
- Correlation of telomere length and DNA damage markers with severity and associated depressive states in patients with OSAS.Frontiers in neurology · 2025Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Aberrant DNA/RNA hybrids (R-loops) formed during transcription and replication disturbances pose threats to genome stability. DHX9 is an RNA helicase involved in R-loop resolution, but how DHX9 is regulated in response to genotoxic stress remains unclear. Here we report that DHX9 is phosphorylated at S321 and S688, with S321 phosphorylation primarily induced by ATR after DNA damage. Phosphorylation of DHX9 at S321 promotes its interaction with γH2AX, BRCA1 and RPA, and is required for its association with R-loops under genotoxic stress. Inhibition of ATR or expression of the non-phosphorylatable DHX9S321A prevents DHX9 from interacting with RPA and R-loops, leading to the accumulation of stress-induced R-loops. Furthermore, depletion of RPA reduces the association between DHX9 and γH2AX, and in vitro binding analysis confirms a direct interaction between DHX9 and RPA. Notably, cells with the non-phosphorylatable DHX9S321A variant exhibit hypersensitivity to genotoxic stress, while those expressing the phosphomimetic DHX9S321D variant prevent R-loop accumulation and display resistance to DNA damage agents. In summary, we uncover a new mechanism by which ATR directly regulates DHX9 through phosphorylation to eliminate stress-induced R-loops.
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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 OpenQuestion graph.