ArticleScience advances2021
FAN1-MLH1 interaction affects repair of DNA interstrand cross-links and slipped-CAG/CTG repeats.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 41 citations in OpenAlex.
- Structural insights into the MLH1-FAN1 interaction reveal an uncharacterized binding interface on MLH1.Nature communications · 2026Article
- USP7 deubiquitinase stabilizes FAN1 to support DNA crosslink repair and suppress CAG repeat expansion.Nature communications · 2026Article
- Mismatch repair MLH complexes make distinct contributions to post-replicative mismatch repair versus trinucleotide repeat expansions.bioRxiv : the preprint server for biology · 2026Article
- Huntington disease: somatic expansion, pathobiology and therapeutics.Nature reviews. Neurology · 2026Review
- Human MutLα activates methylpurine DNA glycosylase to induce alkylation damage cytotoxicity.bioRxiv : the preprint server for biology · 2025Article
- Natural products proposed for the management of Huntington's disease (HD): a comprehensive review.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Disruption of protein-protein interaction hotspots in the C-terminal domain of MLH1 confers mismatch repair deficiency.NAR cancer · 2025Article
- DNA extrusion size determines pathway choice during CAG repeat expansion.Nucleic acids research · 2025Article
- Myotonic dystrophy type 1: clinical diversity, molecular insights and therapeutic perspectives.Nature reviews. Neurology · 2025Review
- Mechanism of trinucleotide repeat expansion by MutSβ-MutLγ and contraction by FAN1.Nature communications · 2025Article
- Emerging drivers of DNA repeat expansions.Biochemical Society transactions · 2025Review
- Comprehensive genetic and epigenetic characterization of Lynch-like syndrome patients.International journal of cancer · 2025Article
- Comprehensive review on Fanconi anemia: insights into DNA interstrand cross-links, repair pathways, and associated tumors.Orphanet journal of rare diseases · 2025Review
- CellPHIE: Integrating Pathway Discovery With Pooled Profiling of Perturbations Uncovers Pathways of Huntington's Disease, Including Genetic Modifiers of Neuronal Development and Morphology.bioRxiv : the preprint server for biology · 2025Article
- A FAN1 point mutation associated with accelerated Huntington's disease progression alters its PCNA-mediated assembly on DNA.Nature communications · 2025Article
- Genomic and Transcriptomic Approaches Advance the Diagnosis and Prognosis of Neurodegenerative Diseases.Genes · 2025Review
- Repair of genomic interstrand crosslinks.DNA repair · 2024Review
- Review
- Posttranscriptional regulation ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Attenuated huntingtin gene CAG nucleotide repeat size in individuals with Lynch syndrome.Scientific reports · 2024Article
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
FAN1, a DNA structure-specific nuclease, interacts with MLH1, but the repair pathways in which this complex acts are unknown. FAN1 processes DNA interstrand crosslinks (ICLs) and FAN1 variants are modifiers of the neurodegenerative Huntington's disease (HD), presumably by regulating HD-causing CAG repeat expansions. Here, we identify specific amino acid residues in two adjacent FAN1 motifs that are critical for MLH1 binding. Disruption of the FAN1-MLH1 interaction confers cellular hypersensitivity to ICL damage and defective repair of CAG/CTG slip-outs, intermediates of repeat expansion mutations. FAN1-S126 phosphorylation, which hinders FAN1-MLH1 association, is cell cycle-regulated by cyclin-dependent kinase activity and attenuated upon ICL induction. Our data highlight the FAN1-MLH1 complex as a phosphorylation-regulated determinant of ICL response and repeat stability, opening novel paths to modify cancer and neurodegeneration.
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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.