ArticleThe EMBO journal2014
Rad17 recruits the MRE11-RAD50-NBS1 complex to regulate the cellular response to DNA double-strand breaks.
Article in The EMBO journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 92 citations in OpenAlex.
- Targeting E3 ubiquitin ligases: Mechanistic breakthroughs and novel clinical translation pathways for tumor radioimmunotherapy.Molecular cancer · 2026Review
- Energetically equivalent structural transitions in the Rad17-Rad9-Hus1-Rad1-Rhino complex underlie the sequential progression from activation through maintenance to inactivation of the ATR-dependent DNA damage response.Nucleic acids research · 2026Article
- Loss of E3 ligase HvST1 function substantially increases distal crossover frequency.The New phytologist · 2026Article
- Review
- βTrCP facilitates MRN complex localization on chromatin to enhance DNA repair.Communications biology · 2025Article
- FOXD3 promotes homologous recombination repair and genomic stability by facilitating MRE11-mediated DNA end resection.Acta biochimica et biophysica Sinica · 2025Article
- Biochemical Mechanisms of Genetic Recombination and DNA Repair.Annual review of biochemistry · 2025Review
- Identification of RAD17 as a candidate cancer predisposition gene in families with histories of pancreatic and breast cancers.BMC cancer · 2024Article
- Review
- Genomic consequences associated with Agrobacterium-mediated transformation of plants.The Plant journal : for cell and molecular biology · 2024Review
- The abscission checkpoint senses chromatin bridges through Top2α recruitment to DNA knots.The Journal of cell biology · 2023Article
- The molecular details of a novel phosphorylation-dependent interaction between MRN and the SOSS complex.Protein science : a publication of the Protein Society · 2023Article
- TLK1-mediated RAD54 phosphorylation spatio-temporally regulates Homologous Recombination Repair.Nucleic acids research · 2023Article
- Regulation of gene editing using T-DNA concatenation.Nature plants · 2023Article
- Cisplatin-induced cell death increases the degradation of the MRE11-RAD50-NBS1 complex through the autophagy/lysosomal pathway.Cell death and differentiation · 2023Article
- TRIM24 is critical for the cellular response to DNA double-strand breaks through regulating the recruitment of MRN complex.Oncogene · 2023Article
- RNF126-Mediated MRE11 Ubiquitination Activates the DNA Damage Response and Confers Resistance of Triple-Negative Breast Cancer to Radiotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Rad17 Translocates to Nucleolus upon UV Irradiation through Nucleolar Localization Signal in the Central Basic Domain.International journal of molecular sciences · 2022Article
- The Role of the TSK/TONSL-H3.1 Pathway in Maintaining Genome Stability in Multicellular Eukaryotes.International journal of molecular sciences · 2022Review
- Structure of the human RAD17-RFC clamp loader and 9-1-1 checkpoint clamp bound to a dsDNA-ssDNA junction.Nucleic acids research · 2022Article
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9 authors at 3 institutions in 1 country.
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Abstract
The MRE11-RAD50-NBS1 (MRN) complex is essential for the detection of DNA double-strand breaks (DSBs) and initiation of DNA damage signaling. Here, we show that Rad17, a replication checkpoint protein, is required for the early recruitment of the MRN complex to the DSB site that is independent of MDC1 and contributes to ATM activation. Mechanistically, Rad17 is phosphorylated by ATM at a novel Thr622 site resulting in a direct interaction of Rad17 with NBS1, facilitating recruitment of the MRN complex and ATM to the DSB, thereby enhancing ATM signaling. Repetition of these events creates a positive feedback for Rad17-dependent activation of MRN/ATM signaling which appears to be a requisite for the activation of MDC1-dependent MRN complex recruitment. A point mutation of the Thr622 residue of Rad17 leads to a significant reduction in MRN/ATM signaling and homologous recombination repair, suggesting that Thr622 phosphorylation is important for regulation of the MRN/ATM signaling by Rad17. These findings suggest that Rad17 plays a critical role in the cellular response to DNA damage via regulation of the MRN/ATM pathway.
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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.