ArticleProceedings of the National Academy of Sciences of the United States of America2020
Human MutLγ, the MLH1-MLH3 heterodimer, is an endonuclease that promotes DNA expansion.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 82 citations in OpenAlex.
- Redundant mispair excision mechanisms in eukaryotic DNA mismatch repair.Nucleus (Austin, Tex.) · 2026Review
- Pharmacologic Inhibition of PMS2 Induces MMR Deficiency and Response to Immune Checkpoint Blockade.Cancer discovery · 2026Article
- Reconciling the effects of PMS2 in different repeat expansion disease models supports a common expansion mechanism.PNAS nexus · 2026Article
- Identification of non-synonymous SNPs affecting structure and function of MLH1 and NBN proteins: a computational approach.Journal of applied genetics · 2026Article
- Mechanism of MutLβ-dependent DNA expansions.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Maternal MLH3 dysfunction drives unexplained recurrent pregnancy loss via impaired oocyte maturation and defective decidualization.Cellular and molecular life sciences : CMLS · 2026Article
- Genetic or pharmacological disruption of the MSH3 Y245/K246 IDL binding pocket slows CAG repeat expansion.NAR molecular medicine · 2026Article
- Mismatch repair MLH complexes make distinct contributions to post-replicative mismatch repair versus trinucleotide repeat expansions.bioRxiv : the preprint server for biology · 2026Article
- MSH3 is a genetic modifier of somatic repeat instability in X-linked dystonia parkinsonism.American journal of human genetics · 2026Article
- Huntington disease: somatic expansion, pathobiology and therapeutics.Nature reviews. Neurology · 2026Review
- The GHKL ATPase Family as a Paradigm for MutL Homolog Function in DNA Mismatch Repair.International journal of molecular sciences · 2025Review
- Disruption of protein-protein interaction hotspots in the C-terminal domain of MLH1 confers mismatch repair deficiency.NAR cancer · 2025Article
- How DNA secondary structures drive replication fork instability.DNA repair · 2025Review
- Mechanism of trinucleotide repeat expansion by MutSβ-MutLγ and contraction by FAN1.Nature communications · 2025Article
- RNA/DNA-binding protein TDP43 regulates DNA mismatch repair genes with implications for genome stability.Nucleic acids research · 2025Article
- RNA/DNA Binding Protein TDP43 Regulates DNA Mismatch Repair Genes with Implications for Genome Stability.bioRxiv : the preprint server for biology · 2025Article
- Msh2-Msh3 DNA-binding is not sufficient to promote trinucleotide repeat expansions in Saccharomyces cerevisiae.Genetics · 2025Article
- Repeat expansion in a fragile X model is independent of double strand break repair mediated by Pol θ, RAD52, RAD54 or RAD54B.Scientific reports · 2025Article
- In vivo CRISPR-Cas9 genome editing in mice identifies genetic modifiers of somatic CAG repeat instability in Huntington's disease.Nature genetics · 2025Article
- 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
2 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 1 country.
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Abstract
MutL proteins are ubiquitous and play important roles in DNA metabolism. MutLγ (MLH1-MLH3 heterodimer) is a poorly understood member of the eukaryotic family of MutL proteins that has been implicated in triplet repeat expansion, but its action in this deleterious process has remained unknown. In humans, triplet repeat expansion is the molecular basis for ∼40 neurological disorders. In addition to MutLγ, triplet repeat expansion involves the mismatch recognition factor MutSβ (MSH2-MSH3 heterodimer). We show here that human MutLγ is an endonuclease that nicks DNA. Strikingly, incision of covalently closed, relaxed loop-containing DNA by human MutLγ is promoted by MutSβ and targeted to the strand opposite the loop. The resulting strand break licenses downstream events that lead to a DNA expansion event in human cell extracts. Our data imply that the mammalian MutLγ is a unique endonuclease that can initiate triplet repeat DNA expansions.
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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.