ArticleGenes & development2008
Mutations in String/CDC25 inhibit cell cycle re-entry and neurodegeneration in a Drosophila model of Ataxia telangiectasia.
Article in Genes & development, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Wings of Discovery: UsingCells · 2025Review
- ATM Kinase Small Molecule Inhibitors Prevent Radiation-Induced Apoptosis of Mouse Neurons In Vivo.Kinases and phosphatases · 2024Article
- Cell cycle re-entry in the agingbioRxiv : the preprint server for biology · 2024Article
- Inherited C-terminal TREX1 variants disrupt homology-directed repair to cause senescence and DNA damage phenotypes in Drosophila, mice, and humans.Nature communications · 2024Article
- Antagonistic effect of cyclin-dependent kinases and a calcium-dependent phosphatase on polyglutamine-expanded androgen receptor toxic gain of function.Science advances · 2023Article
- Regulation of neuronal bioenergetics as a therapeutic strategy in neurodegenerative diseases.Neural regeneration research · 2021Article
- Cell Cycle Re-entry in the Nervous System: From Polyploidy to Neurodegeneration.Frontiers in cell and developmental biology · 2021Review
- Polyploidy in the adulteLife · 2020Article
- Review
- Role of Serotonin Transporter in Eye Development ofInternational journal of molecular sciences · 2020Article
- Modeling Neurodegenerative Disorders inInternational journal of molecular sciences · 2020Review
- Evidence for premature aging in a Drosophila model of Werner syndrome.Experimental gerontology · 2019Article
- A pharmacological screen for compounds that rescue the developmental lethality of a Drosophila ATM mutant.PloS one · 2018Article
- Targeting New Candidate Genes by Small Molecules Approaching Neurodegenerative Diseases.International journal of molecular sciences · 2015Review
- A novel porcine model of ataxia telangiectasia reproduces neurological features and motor deficits of human disease.Human molecular genetics · 2015Article
- Physiological and pathophysiological functions of cell cycle proteins in post-mitotic neurons: implications for Alzheimer's disease.Acta neuropathologica · 2015Review
- EZH2-mediated H3K27 trimethylation mediates neurodegeneration in ataxia-telangiectasia.Nature neuroscience · 2013Article
- ATM and the epigenetics of the neuronal genome.Mechanisms of ageing and development · 2013Review
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Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in ATM (Ataxia telangiectasia mutated) result in Ataxia telangiectasia (A-T), a disorder characterized by progressive neurodegeneration. Despite advances in understanding how ATM signals cell cycle arrest, DNA repair, and apoptosis in response to DNA damage, it remains unclear why loss of ATM causes degeneration of post-mitotic neurons and why the neurological phenotype of ATM-null individuals varies in severity. To address these issues, we generated a Drosophila model of A-T. RNAi knockdown of ATM in the eye caused progressive degeneration of adult neurons in the absence of exogenously induced DNA damage. Heterozygous mutations in select genes modified the neurodegeneration phenotype, suggesting that genetic background underlies variable neurodegeneration in A-T. The neuroprotective activity of ATM may be negatively regulated by deacetylation since mutations in a protein deacetylase gene, RPD3, suppressed neurodegeneration, and a human homolog of RPD3, histone deacetylase 2, bound ATM and abrogated ATM activation in cell culture. Moreover, knockdown of ATM in post-mitotic neurons caused cell cycle re-entry, and heterozygous mutations in the cell cycle activator gene String/CDC25 inhibited cell cycle re-entry and neurodegeneration. Thus, we hypothesize that ATM performs a cell cycle checkpoint function to protect post-mitotic neurons from degeneration and that cell cycle re-entry causes neurodegeneration in A-T.
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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.