ArticleNucleic acids research2024
Pathogenic CANVAS (AAGGG)n repeats stall DNA replication due to the formation of alternative DNA structures.
Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Pentanucleotide guanine-rich WGGGW repeats, including CANVAS AGGGA repeats, form a variety of noncanonical structures.Nucleic acids research · 2026Article
- Dynamic Assemblies in Genome Maintenance.Advances in experimental medicine and biology · 2026Review
- Base excision repair within structure-forming repeat sequences and its impact on cancer and other diseases.NAR cancer · 2025Review
- FGF14 repeat length and mosaic interruptions: modifiers of spinocerebellar ataxia 27B?Brain : a journal of neurology · 2025Article
- Overcoming natural replication barriers formed by DNA structures and the role of repositioning to the nuclear periphery.DNA repair · 2025Review
- Emerging drivers of DNA repeat expansions.Biochemical Society transactions · 2025Review
- The Influence of CG sites on dynamic DNA sequence mutagenesis in the genomic evolution of mammalian lifespan.Nucleic acids research · 2025Article
- Ribosomal DNA arrays are the most H-DNA rich element in the human genome.NAR genomics and bioinformatics · 2025Article
- Triplex H-DNA structure: the long and winding road from the discovery to its role in human disease.NAR molecular medicine · 2024Article
- Article
- Structural polymorphism of the nucleic acids in pentanucleotide repeats associated with the neurological disorder CANVAS.The Journal of biological chemistry · 2024Article
- Detection of alternative DNA structures and its implications for human disease.Molecular cell · 2023Review
Corrections and comments
- Update of
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
CANVAS is a recently characterized repeat expansion disease, most commonly caused by homozygous expansions of an intronic (A2G3)n repeat in the RFC1 gene. There are a multitude of repeat motifs found in the human population at this locus, some of which are pathogenic and others benign. In this study, we conducted structure-functional analyses of the pathogenic (A2G3)n and nonpathogenic (A4G)n repeats. We found that the pathogenic, but not the nonpathogenic, repeat presents a potent, orientation-dependent impediment to DNA polymerization in vitro. The pattern of the polymerization blockage is consistent with triplex or quadruplex formation in the presence of magnesium or potassium ions, respectively. Chemical probing of both repeats in vitro reveals triplex H-DNA formation by only the pathogenic repeat. Consistently, bioinformatic analysis of S1-END-seq data from human cell lines shows preferential H-DNA formation genome-wide by (A2G3)n motifs over (A4G)n motifs. Finally, the pathogenic, but not the nonpathogenic, repeat stalls replication fork progression in yeast and human cells. We hypothesize that the CANVAS-causing (A2G3)n repeat represents a challenge to genome stability by folding into alternative DNA structures that stall DNA replication.
Indexed as
Identifiers
What OpenQuestion holds
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.