Evidence map›Paper›PMID 34469738›Full record

ArticleCell reports2021

FAN1 controls mismatch repair complex assembly via MLH1 retention to stabilize CAG repeat expansion in Huntington's disease.

Robert Goold, Joseph Hamilton, Thomas Menneteau, Michael Flower, Emma L Bunting, Sarah G Aldous, Antonio Porro, José R Vicente, Nicholas D Allen, Hilary Wilkinson and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
5.2field-weighted citation impact, top 3% 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

52 citing papers in PubMed, 77 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Update on Genetic Chorea.Current neurology and neuroscience reports · 2026
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Decoding Huntington's disease: a global survey on symptoms and genetic testing practices.European archives of psychiatry and clinical neuroscience · 2025
    Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Emerging drivers of DNA repeat expansions.Biochemical Society transactions · 2025
    Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 8 institutions in 3 countries.

Robert GooldUCL Huntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK; UK Dementia Research Institute, University College London, London WC1N 3BG, UK.
Joseph HamiltonUCL Huntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK; UK Dementia Research Institute, University College London, London WC1N 3BG, UK.
Thomas MenneteauUK Dementia Research Institute, University College London, London WC1N 3BG, UK; Institute of Structural and Molecular Biology, Division of Biosciences, University College London, London WC1E 6BT, UK.
Michael FlowerUCL Huntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK; UK Dementia Research Institute, University College London, London WC1N 3BG, UK.
Emma L BuntingUCL Huntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Sarah G AldousUCL Huntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK; UK Dementia Research Institute, University College London, London WC1N 3BG, UK.
Antonio PorroInstitute of Molecular Cancer Research, University of Zurich, Zurich 8057, Switzerland.
José R VicenteUK Dementia Research Institute, University of Cambridge, Cambridge CB2 0AH, UK.
Nicholas D AllenSchool of Biosciences, Cardiff University, Cardiff CF10 3AX, UK.
Hilary WilkinsonCHDI Management/CHDI Foundation, Princeton, NJ 08540, USA.
Gillian P BatesUCL Huntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK; UK Dementia Research Institute, University College London, London WC1N 3BG, UK.
Alessandro A SartoriInstitute of Molecular Cancer Research, University of Zurich, Zurich 8057, Switzerland.
Konstantinos ThalassinosInstitute of Structural and Molecular Biology, Division of Biosciences, University College London, London WC1E 6BT, UK; Institute of Structural and Molecular Biology, Birkbeck College, University of London, London WC1E 7HX, UK.
Gabriel BalmusUK Dementia Research Institute, University of Cambridge, Cambridge CB2 0AH, UK; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0AH, UK. Electronic address: gb318@cam.ac.uk.
Sarah J TabriziUCL Huntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK; UK Dementia Research Institute, University College London, London WC1N 3BG, UK. Electronic address: s.tabrizi@ucl.ac.uk.
UK Dementia Research Institute · GBUniversity College London · GBNational Hospital for Neurology and Neurosurgery · GBUniversity of Cambridge · GBUniversity of Zurich · CHCardiff University · GBCHDI Foundation · USInstitute of Structural and Molecular Biology · GB

Funding

Medical Research Council MR/L023784/2Wellcome TrustWellcome Trust 200181/Z/15/Z
6 · The paper itself

Abstract

CAG repeat expansion in the HTT gene drives Huntington's disease (HD) pathogenesis and is modulated by DNA damage repair pathways. In this context, the interaction between FAN1, a DNA-structure-specific nuclease, and MLH1, member of the DNA mismatch repair pathway (MMR), is not defined. Here, we identify a highly conserved SPYF motif at the N terminus of FAN1 that binds to MLH1. Our data support a model where FAN1 has two distinct functions to stabilize CAG repeats. On one hand, it binds MLH1 to restrict its recruitment by MSH3, thus inhibiting the assembly of a functional MMR complex that would otherwise promote CAG repeat expansion. On the other hand, it promotes accurate repair via its nuclease activity. These data highlight a potential avenue for HD therapeutics in attenuating somatic expansion.

Indexed as

DNA DamageDNA Mismatch RepairTrinucleotide Repeat ExpansionAnimalsBinding, CompetitiveBrainCell Line, TumorEndodeoxyribonucleasesExodeoxyribonucleasesHEK293 CellsHumansHuntingtin ProteinHuntington DiseaseMiceMultifunctional EnzymesMutL Protein Homolog 1EndodeoxyribonucleasesExodeoxyribonucleasesFAN1 protein, humanFan1 protein, mouseHTT protein, humanHuntingtin ProteinMLH1 protein, humanMlh1 protein, mouseMSH3 protein, humanMultifunctional EnzymesMutL Protein Homolog 1MutS Homolog 3 ProteinCAG instabilityDNA repairFAN1FAN1 nuclease activityGWASHuntington’s diseasemismatch repairMLH1MSH3repeat expansion

Identifiers

PMID34469738
PMCPMC8424649
OpenAlexW3198419829

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.