ArticleNature communications2024
DTX3L-mediated TIRR nuclear export and degradation regulates DNA repair pathway choice and PARP inhibitor sensitivity.
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 10 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed.
- SPOP-mediated ZMYND8 ubiquitination and phase separation exclusion drives mTOR inhibitor resistance in kidney cancer.Nature communications · 2026Article
- Loss of CYLD on Chromosome 16q Impairs Homologous Recombination and Genomic Stability Through TIRR Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- DTX3L Inhibits the EMT, Metastasis, and Stem-Like Features of Gastric Cancer Through Promoting GSK-3β Dependent SNAI1 Decay.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CHD1L maintains genome integrity by facilitating okazaki fragment maturation.Nucleic acids research · 2026Article
- Chromatin Remodeling, DNA Double-Strand Break Repair, and Human Disease: How a Breakup Changes You.Biomolecules · 2026Review
- DTX3L promotes ovarian cancer progression and cisplatin resistance by activating JAK1/STAT1/OAS3 pathway.Scientific reports · 2026Article
- Interplay Between Poly(ADP-ribosyl)ation and Specific Inner Cellular Events That Suggest Combination Strategies for Overcoming PARP Inhibitor Resistance.Pharmaceutics · 2026Review
- LINC00973/DTX3L Axis Promotes Non-Small Cell Lung Cancer Progression and Serves as a Therapeutic Target.Smart medicine · 2026Article
- Investigating the functions and molecular mechanisms of DTX3L in cancer progression.Frontiers in oncology · 2026Review
- Non-Histone Lysine Modifications in Tumor Microenvironment: Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2025Review
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
53BP1 plays an important role in DNA double-strand break (DSB) repair and this activity is negatively regulated by its interaction with Tudor interacting repair regulator (TIRR). However, how the TIRR-53BP1 repair axis is regulated in response to DNA damage remains elusive. Here, we demonstrate that TIRR is translocated to the cytoplasm and degraded upon DNA damage. Ubiquitination of TIRR at lysine 187 by DTX3L is a critical process that regulates NHEJ pathway activity and PARP inhibitor sensitivity by facilitating XPO1-mediated TIRR nuclear export and degradation after DNA damage. We show that DTX3L is overexpressed in prostate cancers in patients and that decreased expression of TIRR due to DTX3L overexpression impairs the negative regulatory effect of TIRR on 53BP1, which consequently induces HR deficiency and chromosomal instability and sensitizes prostate cancer cells to poly (ADP-ribose) polymerase (PARP) inhibitors. Our work reveals a dual action of DTX3L on TIRR degradation and nuclear exportation and identifies DTX3L as an upstream regulator of the TIRR-53BP1 axis that governs DNA repair pathway choice and PARP inhibitor sensitivity. These findings suggest that TIRR ubiquitination and DTX3L overexpression could be viable biomarkers predicting PARP inhibitor sensitivity in cancers.
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Registered trials
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