ArticleBiochemistry2012
The nucleotide sequence, DNA damage location, and protein stoichiometry influence the base excision repair outcome at CAG/CTG repeats.
Article in Biochemistry, 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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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
28 citing papers in PubMed, 44 citations in OpenAlex.
- APOBEC3A deaminates CTG hairpin loops to promote fragility and instability of expanded CAG/CTG repeats.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- CRISPR/Cas9-induced double-strand breaks in the huntingtin locus lead to CAG repeat contraction through DNA end resection and homology-mediated repair.BMC biology · 2024Article
- Article
- The RNA export and RNA decay complexes THO and TRAMP prevent transcription-replication conflicts, DNA breaks, and CAG repeat contractions.PLoS biology · 2022Article
- FAN1, a DNA Repair Nuclease, as a Modifier of Repeat Expansion Disorders.Journal of Huntington's disease · 2021Review
- Exploring the role of high-mobility group box 1 (HMGB1) protein in the pathogenesis of Huntington's disease.Journal of molecular medicine (Berlin, Germany) · 2020Review
- Dynamic DNA Energy Landscapes and Substrate Complexity in Triplet Repeat Expansion and DNA Repair.Biomolecules · 2019Article
- PGC-1α, Sirtuins and PARPs in Huntington's Disease and Other Neurodegenerative Conditions: NAD+ to Rule Them All.Neurochemical research · 2019Review
- An oxidized abasic lesion inhibits base excision repair leading to DNA strand breaks in a trinucleotide repeat tract.PloS one · 2018Article
- Oxidized dNTPs and the OGG1 and MUTYH DNA glycosylases combine to induce CAG/CTG repeat instability.Nucleic acids research · 2016Article
- A 5', 8-cyclo-2'-deoxypurine lesion induces trinucleotide repeat deletion via a unique lesion bypass by DNA polymerase β.Nucleic acids research · 2014Article
- Impact of alternative DNA structures on DNA damage, DNA repair, and genetic instability.DNA repair · 2014Review
- APE1 incision activity at abasic sites in tandem repeat sequences.Journal of molecular biology · 2014Article
- 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.Human molecular genetics · 2014Article
- Impact of bulge loop size on DNA triplet repeat domains: Implications for DNA repair and expansion.Biopolymers · 2014Article
- Review
- Mismatch repair genes Mlh1 and Mlh3 modify CAG instability in Huntington's disease mice: genome-wide and candidate approaches.PLoS genetics · 2013Article
- Article
- The 26S proteasome drives trinucleotide repeat expansions.Nucleic acids research · 2013Article
- DNA repair mechanisms in Huntington's disease.Molecular neurobiology · 2013Review
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
Abstract
Expansion of CAG/CTG repeats is the underlying cause of >14 genetic disorders, including Huntington's disease (HD) and myotonic dystrophy. The mutational process is ongoing, with increases in repeat size enhancing the toxicity of the expansion in specific tissues. In many repeat diseases, the repeats exhibit high instability in the striatum, whereas instability is minimal in the cerebellum. We provide molecular insights into how base excision repair (BER) protein stoichiometry may contribute to the tissue-selective instability of CAG/CTG repeats by using specific repair assays. Oligonucleotide substrates with an abasic site were mixed with either reconstituted BER protein stoichiometries mimicking the levels present in HD mouse striatum or cerebellum, or with protein extracts prepared from HD mouse striatum or cerebellum. In both cases, the repair efficiency at CAG/CTG repeats and at control DNA sequences was markedly reduced under the striatal conditions, likely because of the lower level of APE1, FEN1, and LIG1. Damage located toward the 5' end of the repeat tract was poorly repaired, with the accumulation of incompletely processed intermediates as compared to an AP lesion in the center or at the 3' end of the repeats or within control sequences. Moreover, repair of lesions at the 5' end of CAG or CTG repeats involved multinucleotide synthesis, particularly at the cerebellar stoichiometry, suggesting that long-patch BER processes lesions at sequences susceptible to hairpin formation. Our results show that the BER stoichiometry, nucleotide sequence, and DNA damage position modulate repair outcome and suggest that a suboptimal long-patch BER activity promotes CAG/CTG repeat instability.
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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.