ArticleNucleic acids research2017
Homeostatic nuclear RAGE-ATM interaction is essential for efficient DNA repair.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 82 citations in OpenAlex.
- Epigenome-wide Mendelian randomization with multi-omics validation identifies epigenetic drivers of idiopathic pulmonary fibrosis.Communications biology · 2026Article
- The Influence of Body Mass Index on Biomarkers of Cellular Senescence in Older Adults.The journals of gerontology. Series A, Biological sciences and medical sciences · 2025Article
- Targeting the AGEs-RAGE axis: pathogenic mechanisms and therapeutic interventions in diabetic wound healing.Frontiers in medicine · 2025Review
- Longitudinal microcomputed tomography detects onset and progression of pulmonary fibrosis in conditionalAmerican journal of physiology. Lung cellular and molecular physiology · 2024Article
- Cell Proliferation and Apoptosis-Key Players in the Lung Aging Process.International journal of molecular sciences · 2024Review
- Article
- YTHDC1 delays cellular senescence and pulmonary fibrosis by activating ATR in an m6A-independent manner.The EMBO journal · 2024Article
- Glycation in the cardiomyocyte.Vitamins and hormones · 2024Review
- Cigarette Smoke-Induced Respiratory Response: Insights into Cellular Processes and Biomarkers.Antioxidants (Basel, Switzerland) · 2023Review
- The AGE-RAGE Axis and the Pathophysiology of Multimorbidity in COPD.Journal of clinical medicine · 2023Review
- Biomarkers of cellular senescence in idiopathic pulmonary fibrosis.Respiratory research · 2023Article
- The importance of nuclear RAGE-Mcm2 axis in diabetes or cancer-associated replication stress.Nucleic acids research · 2023Article
- A novel DNA double-strand breaks biosensor based on fluorescence resonance energy transfer.Biomaterials research · 2023Article
- Analysis of the Potential Relationship between Aging and Pulmonary Fibrosis Based on Transcriptome.Life (Basel, Switzerland) · 2022Article
- Effects of RAGE Deletion on the Cardiac Transcriptome during Aging.International journal of molecular sciences · 2022Article
- A Fast and Reliable Method to Generate Pure, Single Cell-derived Clones of Mammalian Cells.Bio-protocol · 2022Article
- The RAGE/multiligand axis: a new actor in tumor biology.Bioscience reports · 2022Review
- Skin Fibrosis and Recovery Is Dependent on Wnt Activation via DPP4.The Journal of investigative dermatology · 2022Article
- Role and Therapeutic Potential of RAGE Signaling in Neurodegeneration.Current drug targets · 2022Article
- Pathophysiology of RAGE in inflammatory diseases.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
22 authors at 12 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The integrity of genome is a prerequisite for healthy life. Indeed, defects in DNA repair have been associated with several human diseases, including tissue-fibrosis, neurodegeneration and cancer. Despite decades of extensive research, the spatio-mechanical processes of double-strand break (DSB)-repair, especially the auxiliary factor(s) that can stimulate accurate and timely repair, have remained elusive. Here, we report an ATM-kinase dependent, unforeseen function of the nuclear isoform of the Receptor for Advanced Glycation End-products (nRAGE) in DSB-repair. RAGE is phosphorylated at Serine376 and Serine389 by the ATM kinase and is recruited to the site of DNA-DSBs via an early DNA damage response. nRAGE preferentially co-localized with the MRE11 nuclease subunit of the MRN complex and orchestrates its nucleolytic activity to the ATR kinase signaling. This promotes efficient RPA2S4-S8 and CHK1S345 phosphorylation and thereby prevents cellular senescence, IPF and carcinoma formation. Accordingly, loss of RAGE causatively linked to perpetual DSBs signaling, cellular senescence and fibrosis. Importantly, in a mouse model of idiopathic pulmonary fibrosis (RAGE-/-), reconstitution of RAGE efficiently restored DSB-repair and reversed pathological anomalies. Collectively, this study identifies nRAGE as a master regulator of DSB-repair, the absence of which orchestrates persistent DSB signaling to senescence, tissue-fibrosis and oncogenesis.
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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.