Evidence map›Paper›PMID 33579859›Full record

ReviewJournal of Huntington's disease2021

DNA Repair in Huntington's Disease and Spinocerebellar Ataxias: Somatic Instability and Alternative Hypotheses.

Tamara Maiuri, Claudia L K Hung, Celeste Suart, Nola Begeja, Carlos Barba-Bazan, Yi Peng, Natasha Savic, Timothy Wong, Ray Truant

Open access · bronzeAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Journal of Huntington's disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.8field-weighted citation impact, top 17% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Sulfide regulation and catabolism in health and disease.Signal transduction and targeted therapy · 2025
    Review
  5. Article
  6. Review
  7. Poly ADP-ribose signaling is dysregulated in Huntington disease.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  8. Review
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  13. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Tamara MaiuriMcMaster University, Department of Biochemistry and Biomedical Sciences, Hamilton, Ontario, Canada.
Claudia L K HungMcMaster University, Department of Biochemistry and Biomedical Sciences, Hamilton, Ontario, Canada.
Celeste SuartMcMaster University, Department of Biochemistry and Biomedical Sciences, Hamilton, Ontario, Canada.
Nola BegejaMcMaster University, Department of Biochemistry and Biomedical Sciences, Hamilton, Ontario, Canada.
Carlos Barba-BazanMcMaster University, Department of Biochemistry and Biomedical Sciences, Hamilton, Ontario, Canada.
Yi PengMcMaster University, Department of Biochemistry and Biomedical Sciences, Hamilton, Ontario, Canada.
Natasha SavicMcMaster University, Department of Biochemistry and Biomedical Sciences, Hamilton, Ontario, Canada.
Timothy WongMcMaster University, Department of Biochemistry and Biomedical Sciences, Hamilton, Ontario, Canada.
Ray TruantMcMaster University, Department of Biochemistry and Biomedical Sciences, Hamilton, Ontario, Canada.
McMaster University · CA

Funding

CIHR
6 · The paper itself

Abstract

The use of genome wide association studies (GWAS) in Huntington's disease (HD) research, driven by unbiased human data analysis, has transformed the focus of new targets that could affect age at onset. While there is a significant depth of information on DNA damage repair, with many drugs and drug targets, most of this development has taken place in the context of cancer therapy. DNA damage repair in neurons does not rely on DNA replication correction mechanisms. However, there is a strong connection between DNA repair and neuronal metabolism, mediated by nucleotide salvaging and the poly ADP-ribose (PAR) response, and this connection has been implicated in other age-onset neurodegenerative diseases. Validation of leads including the mismatch repair protein MSH3, and interstrand cross-link repair protein FAN1, suggest the mechanism is driven by somatic CAG instability, which is supported by the protective effect of CAA substitutions in the CAG tract. We currently do not understand: how somatic instability is triggered; the state of DNA damage within expanding alleles in the brain; whether this damage induces mismatch repair and interstrand cross-link pathways; whether instability mediates toxicity, and how this relates to human ageing. We discuss DNA damage pathways uncovered by HD GWAS, known roles of other polyglutamine disease proteins in DNA damage repair, and a panel of hypotheses for pathogenic mechanisms.

Indexed as

Genome-Wide Association StudyDNA RepairGenomic InstabilityHumansHuntington DiseaseSpinocerebellar Ataxiasdisease modifiersgenome wide analysis studiesHuntington’s diseaseN6-furfuryladeninesomatic expansion

Identifiers

PMID33579859
PMCPMC7990435
OpenAlexW3128481056

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.