ArticleThe Journal of biological chemistry2015
DNA Replication Dynamics of the GGGGCC Repeat of the C9orf72 Gene.
Article in The Journal of biological chemistry, 2015. 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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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 35 citations in OpenAlex.
- The spectrum ofFrontiers in neuroscience · 2026Article
- Article
- Emerging drivers of DNA repeat expansions.Biochemical Society transactions · 2025Review
- Replicative DNA polymerase epsilon and delta holoenzymes show wide-ranging inhibition at G-quadruplexes in the human genome.Nucleic acids research · 2025Article
- Review
- Bridging the gap: R-loop mediated genomic instability and its implications in neurological diseases.Epigenomics · 2024Review
- The shared ancestry between the C9orf72 hexanucleotide repeat expansion and intermediate-length alleles using haplotype sharing trees and HAPTK.American journal of human genetics · 2024Article
- Replication-induced DNA secondary structures drive fork uncoupling and breakage.The EMBO journal · 2023Article
- Advances in the Structure of GGGGCC Repeat RNA Sequence and Its Interaction with Small Molecules and Protein Partners.Molecules (Basel, Switzerland) · 2023Review
- G-Quadruplexes in Repeat Expansion Disorders.International journal of molecular sciences · 2023Review
- Article
- Response to the letter by de Boer et al. (2022).Acta neuropathologica communications · 2022Article
- Mismatch repair is a double-edged sword in the battle against microsatellite instability.Expert reviews in molecular medicine · 2022Review
- Expanding Clinical Spectrum ofNeurology. Genetics · 2022Review
- Length-dependent RNA foci formation and Repeat Associated non-AUG dependent translation in amicroPublication biology · 2022Article
- G-Quadruplexes in Neurobiology and Virology: Functional Roles and Potential Therapeutic Approaches.JACS Au · 2021Review
- The effects of molecular crowding and CpG hypermethylation on DNA G-quadruplexes formed by the C9orf72 nucleotide repeat expansion.Scientific reports · 2021Article
- Genome-wide association study of frontotemporal dementia identifies a C9ORF72 haplotype with a median of 12-G4C2 repeats that predisposes to pathological repeat expansions.Translational psychiatry · 2021Article
- Sizing, stabilising, and cloning repeat-expansions for gene targeting constructs.Methods (San Diego, Calif.) · 2021Article
- G-Quadruplexes as pathogenic drivers in neurodegenerative disorders.Nucleic acids research · 2021Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
DNA has the ability to form a variety of secondary structures in addition to the normal B-form DNA, including hairpins and quadruplexes. These structures are implicated in a number of neurological diseases and cancer. Expansion of a GGGGCC repeat located at C9orf72 is associated with familial amyotrophic lateral sclerosis and frontotemporal dementia. This repeat expands from two to 24 copies in normal individuals to several hundreds or thousands of repeats in individuals with the disease. Biochemical studies have demonstrated that as little as four repeats have the ability to form a stable DNA secondary structure known as a G-quadruplex. Quadruplex structures have the ability to disrupt normal DNA processes such as DNA replication and transcription. Here we examine the role of GGGGCC repeat length and orientation on DNA replication using an SV40 replication system in human cells. Replication through GGGGCC repeats leads to a decrease in overall replication efficiency and an increase in instability in a length-dependent manner. Both repeat expansions and contractions are observed, and replication orientation is found to influence the propensity for expansions or contractions. The presence of replication stress, such as low-dose aphidicolin, diminishes replication efficiency but has no effect on instability. Two-dimensional gel electrophoresis analysis demonstrates a replication stall with as few as 20 GGGGCC repeats. These results suggest that replication of the GGGGCC repeat at C9orf72 is perturbed by the presence of expanded repeats, which has the potential to result in further expansion, leading to disease.
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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.