ArticleThe Journal of clinical investigation2015
DNA replication stress underlies renal phenotypes in CEP290-associated Joubert syndrome.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 57 citations in OpenAlex.
- Testing the Transferability of Perturbational Similarity Maps Across Species, Cell Systems, and Assay Modalities.Neuroinformatics · 2026Article
- Modeling Complex Developmental Disease: The Case of Polycystic Kidney Disease.Journal of developmental biology · 2026Review
- CEP290 deficiency disrupts ciliary axonemal architecture in human iPSC-derived brain organoids.Journal of cell science · 2025Article
- Hedgehog pathway, cell cycle, and primary cilium.Cell death discovery · 2025Review
- Genome-Based Advances in Modeling Renal Ciliopathies and Enhancing Patient Care.Kidney & blood pressure research · 2025Review
- Nephronophthisis: a pathological and genetic perspective.Pediatric nephrology (Berlin, Germany) · 2024Review
- Pathological consequences of DNA damage in the kidney.Nature reviews. Nephrology · 2023Review
- The importance of nuclear RAGE-Mcm2 axis in diabetes or cancer-associated replication stress.Nucleic acids research · 2023Article
- Nephronophthisis-Pathobiology and Molecular Pathogenesis of a Rare Kidney Genetic Disease.Genes · 2021Review
- Sufu negatively regulates both initiations of centrosome duplication and DNA replication.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Primary cilia biogenesis and associated retinal ciliopathies.Seminars in cell & developmental biology · 2021Review
- Renal Ciliopathies: Sorting Out Therapeutic Approaches for Nephronophthisis.Frontiers in cell and developmental biology · 2021Review
- Disease Modeling To Understand the Pathomechanisms of Human Genetic Kidney Disorders.Clinical journal of the American Society of Nephrology : CJASN · 2020Review
- RNA helicase p68 inhibits the transcription and post-transcription ofTheranostics · 2020Article
- Innate Immune Signaling Contributes to Tubular Cell Senescence in the Glis2 Knockout Mouse Model of Nephronophthisis.The American journal of pathology · 2020Article
- Article
- Therapeutic perspectives for structural and functional abnormalities of cilia.Cellular and molecular life sciences : CMLS · 2019Review
- Opportunities and Challenges for Molecular Understanding of Ciliopathies-The 100,000 Genomes Project.Frontiers in genetics · 2019Review
- Exploring the Role of Fallopian Ciliated Cells in the Pathogenesis of High-Grade Serous Ovarian Cancer.International journal of molecular sciences · 2018Review
- Urine-derived cells: a promising diagnostic tool in Fabry disease patients.Scientific reports · 2018Article
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
Juvenile ciliopathy syndromes that are associated with renal cysts and premature renal failure are commonly the result of mutations in the gene encoding centrosomal protein CEP290. In addition to centrosomes and the transition zone at the base of the primary cilium, CEP290 also localizes to the nucleus; however, the nuclear function of CEP290 is unknown. Here, we demonstrate that reduction of cellular CEP290 in primary human and mouse kidney cells as well as in zebrafish embryos leads to enhanced DNA damage signaling and accumulation of DNA breaks ex vivo and in vivo. Compared with those from WT mice, primary kidney cells from Cep290-deficient mice exhibited supernumerary centrioles, decreased replication fork velocity, fork asymmetry, and increased levels of cyclin-dependent kinases (CDKs). Treatment of Cep290-deficient cells with CDK inhibitors rescued DNA damage and centriole number. Moreover, the loss of primary cilia that results from CEP290 dysfunction was rescued in 3D cell culture spheroids of primary murine kidney cells after exposure to CDK inhibitors. Together, our results provide a link between CEP290 and DNA replication stress and suggest CDK inhibition as a potential treatment strategy for a wide range of ciliopathy syndromes.
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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.