ArticleMolecular neurobiology2012
Deregulation of BRCA1 leads to impaired spatiotemporal dynamics of γ-H2AX and DNA damage responses in Huntington's disease.
Article in Molecular neurobiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- When R-Loops Go Awry: Genome Instability and Neurological Diseases.The European journal of neuroscience · 2026Review
- Engineered chromatin readers track damaged chromatin dynamics in live cells and animals.Nature communications · 2025Article
- Crosstalk between DNA damage and cGAS-STING immune pathway drives neuroinflammation and dopaminergic neurodegeneration in Parkinson's disease.Brain, behavior, and immunity · 2025Article
- Zika virus impairs non-homologous end joining and exacerbates DNA damage in neural progenitors derived from Huntington's disease iPSCs via mutant huntingtin-elicited Ku70/Ku80 complex disruption.Stem cell research & therapy · 2025Article
- Sphingosine kinase 2 regulates protein ubiquitination networks in neurons.Molecular and cellular neurosciences · 2024Article
- Novel Techniques for Mapping DNA Damage and Repair in the Brain.International journal of molecular sciences · 2024Review
- Modulation of Synaptic Plasticity Genes Associated to DNA Damage in a Model of Huntington's Disease.Neurochemical research · 2023Article
- Defective repair of topoisomerase I induced chromosomal damage in Huntington's disease.Cellular and molecular life sciences : CMLS · 2022Article
- The Role of DNA Damage in Neural Plasticity in Physiology and Neurodegeneration.Frontiers in cellular neuroscience · 2022Review
- The Phosphorylated Form of the Histone H2AX (γH2AX) in the Brain from Embryonic Life to Old Age.Molecules (Basel, Switzerland) · 2021Review
- Non-Cell Autonomous and Epigenetic Mechanisms of Huntington's Disease.International journal of molecular sciences · 2021Review
- Article
- Breast cancer type 1 and neurodegeneration: consequences of deficient DNA repair.Brain communications · 2021Review
- DNA Double-Strand Break Accumulation in Alzheimer's Disease: Evidence from Experimental Models and Postmortem Human Brains.Molecular neurobiology · 2021Article
- Activation of TGR5 protects blood brain barrier via the BRCA1/Sirt1 pathway after middle cerebral artery occlusion in rats.Journal of biomedical science · 2020Article
- Colocalization of BRCA1 with Tau Aggregates in Human Tauopathies.Brain sciences · 2019Article
- Emerging Perspectives on DNA Double-strand Breaks in Neurodegenerative Diseases.Current neuropharmacology · 2019Review
- A BRCA1-Dependent DNA Damage Response in the Regenerating Adult Peripheral Nerve Milieu.Molecular neurobiology · 2018Article
- Review
- Inhibiting sphingosine kinase 2 mitigates mutant Huntingtin-induced neurodegeneration in neuron models of Huntington disease.Human molecular genetics · 2017Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder of mid-life onset characterized by involuntary movements and progressive cognitive decline caused by a CAG repeat expansion in exon 1 of the Huntingtin (Htt) gene. Neuronal DNA damage is one of the major features of neurodegeneration in HD, but it is not known how it arises or relates to the triplet repeat expansion mutation in the Htt gene. Herein, we found that imbalanced levels of non-phosphorylated and phosphorylated BRCA1 contribute to the DNA damage response in HD. Notably, nuclear foci of γ-H2AX, the molecular component that recruits various DNA damage repair factors to damage sites including BRCA1, were deregulated when DNA was damaged in HD cell lines. BRCA1 specifically interacted with γ-H2AX via the BRCT domain, and this association was reduced in HD. BRCA1 overexpression restored γ-H2AX level in the nucleus of HD cells, while BRCA1 knockdown reduced the spatiotemporal propagation of γ-H2AX foci to the nucleoplasm. The deregulation of BRCA1 correlated with an abnormal nuclear distribution of γ-H2AX in striatal neurons of HD transgenic (R6/2) mice and BRCA1(+/-) mice. Our data indicate that BRCA1 is required for the efficient focal recruitment of γ-H2AX to the sites of neuronal DNA damage. Taken together, our results show that BRCA1 directly modulates the spatiotemporal dynamics of γ-H2AX upon genotoxic stress and serves as a molecular maker for neuronal DNA damage response in HD.
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