ArticleHuman molecular genetics2014
Expression levels of DNA replication and repair genes predict regional somatic repeat instability in the brain but are not altered by polyglutamine disease protein expression or age.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
30 citing papers in PubMed, 52 citations in OpenAlex.
- Tandem repeats in human brain evolution and disease susceptibility.Molecules and cells · 2026Review
- Emerging drivers of DNA repeat expansions.Biochemical Society transactions · 2025Review
- NOTCH2NLC GGC intermediate repeat with serine induces hypermyelination and early Parkinson's disease-like phenotypes in mice.Molecular neurodegeneration · 2024Article
- Article
- CAG repeat instability in embryonic stem cells and derivative spermatogenic cells of transgenic Huntington's disease monkey.Journal of assisted reproduction and genetics · 2021Article
- TCF4-mediated Fuchs endothelial corneal dystrophy: Insights into a common trinucleotide repeat-associated disease.Progress in retinal and eye research · 2021Review
- Replication-independent instability of Friedreich's ataxia GAA repeats during chronological aging.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Modifiers of CAG/CTG Repeat Instability: Insights from Mammalian Models.Journal of Huntington's disease · 2021Review
- FAN1, a DNA Repair Nuclease, as a Modifier of Repeat Expansion Disorders.Journal of Huntington's disease · 2021Review
- Patterns of CAG repeat instability in the central nervous system and periphery in Huntington's disease and in spinocerebellar ataxia type 1.Human molecular genetics · 2020Article
- On the wrong DNA track: Molecular mechanisms of repeat-mediated genome instability.The Journal of biological chemistry · 2020Review
- Chronic Exposure to Cadmium and Antioxidants Does Not Affect the Dynamics of Expanded CAG•CTG Trinucleotide Repeats in a Mouse Cell Culture System of Unstable DNA.Frontiers in cellular neuroscience · 2020Article
- Characterization of Iron Accumulation in Deep Gray Matter in Myotonic Dystrophy Type 1 and 2 Using Quantitative Susceptibility Mapping and R2Frontiers in neurology · 2019Article
- Cis- and Trans-Modifiers of Repeat Expansions: Blending Model Systems with Human Genetics.Trends in genetics : TIG · 2018Review
- Article
- Repeat expansion diseases.Handbook of clinical neurology · 2018Review
- A Defective mRNA Cleavage and Polyadenylation Complex Facilitates Expansions of Transcribed (GAA)Cell reports · 2017Article
- Phosphate steering by Flap Endonuclease 1 promotes 5'-flap specificity and incision to prevent genome instability.Nature communications · 2017Article
- DNA repair pathways underlie a common genetic mechanism modulating onset in polyglutamine diseases.Annals of neurology · 2016Article
- Absence of MutSβ leads to the formation of slipped-DNA for CTG/CAG contractions at primate replication forks.DNA repair · 2016Article
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Authors and funding
9 authors at 6 institutions in 4 countries.
Funding
Abstract
Expansion of CAG/CTG trinucleotide repeats causes numerous inherited neurological disorders, including Huntington's disease (HD), several spinocerebellar ataxias and myotonic dystrophy type 1. Expanded repeats are genetically unstable with a propensity to further expand when transmitted from parents to offspring. For many alleles with expanded repeats, extensive somatic mosaicism has been documented. For CAG repeat diseases, dramatic instability has been documented in the striatum, with larger expansions noted with advancing age. In contrast, only modest instability occurs in the cerebellum. Using microarray expression analysis, we sought to identify the genetic basis of these regional instability differences by comparing gene expression in the striatum and cerebellum of aged wild-type C57BL/6J mice. We identified eight candidate genes enriched in cerebellum, and validated four--Pcna, Rpa1, Msh6 and Fen1--along with a highly associated interactor, Lig1. We also explored whether expression levels of mismatch repair (MMR) proteins are altered in a line of HD transgenic mice, R6/2, that is known to show pronounced regional repeat instability. Compared with wild-type littermates, MMR expression levels were not significantly altered in R6/2 mice regardless of age. Interestingly, expression levels of these candidates were significantly increased in the cerebellum of control and HD human samples in comparison to striatum. Together, our data suggest that elevated expression levels of DNA replication and repair proteins in cerebellum may act as a safeguard against repeat instability, and may account for the dramatically reduced somatic instability present in this brain region, compared with the marked instability observed in the striatum.
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