ArticlePLoS biology2017
The mismatch repair and meiotic recombination endonuclease Mlh1-Mlh3 is activated by polymer formation and can cleave DNA substrates in trans.
Article in PLoS biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 87 citations in OpenAlex.
- Crossover control: A key to unlocking genetic diversity in plant breeding.Journal of integrative plant biology · 2026Review
- Molecular assessment of recombination processing across genetically diverse mouse strains reveals sexually dimorphic determinants of crossover distribution beyond chromosome length.Molecular biology and evolution · 2026Article
- Mms4 chromosomal association reveals functional relationships between meiotic crossover pathways in budding yeast.PLoS genetics · 2026Article
- Mismatch repair MLH complexes make distinct contributions to post-replicative mismatch repair versus trinucleotide repeat expansions.bioRxiv : the preprint server for biology · 2026Article
- DNA mismatch repair mediated by Mlh1-Pms1 endonuclease-catalyzed mispair excision.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Chromosome length is not the sole determinant of sexually dimorphic crossover rates during mammalian meiosis: Insights from genetically diverse mouse strains.bioRxiv : the preprint server for biology · 2025Article
- The GHKL ATPase Family as a Paradigm for MutL Homolog Function in DNA Mismatch Repair.International journal of molecular sciences · 2025Review
- Aberrant cytoplasmic localization of MLH1 characterizes a cell population that seeds breast cancer recurrence.Nature communications · 2025Article
- Mlh1-Pms1 couples ATP-driven DNA compaction with nick-dependent endonuclease activation.Nucleic acids research · 2025Article
- Mismatch repair disturbs meiotic crossover control in S. cerevisiae.Nucleic acids research · 2025Article
- Article
- Mechanism of trinucleotide repeat expansion by MutSβ-MutLγ and contraction by FAN1.Nature communications · 2025Article
- EXO1 promotes the meiotic MLH1-MLH3 endonuclease through conserved interactions with MLH1, MSH4 and DNA.Nature communications · 2025Article
- Advances in diagnostic and therapeutic applications of mismatch repair loss in cancer.DNA repair · 2025Review
- MutLγ enforces meiotic crossovers in Arabidopsis thaliana.Nucleic acids research · 2025Article
- Mlh1-Pms1 ATPase activity is regulated distinctly by self-generated nicks and strand discrimination signals in mismatch repair.Nucleic acids research · 2025Article
- The mismatch repair factor Mlh1-Pms1 uses ATP to compact and remodel DNA.bioRxiv : the preprint server for biology · 2025Article
- Crossover recombination between homologous chromosomes in meiosis: recent progress and remaining mysteries.Trends in genetics : TIG · 2025Review
- Separable roles of the DNA damage response kinase Mec1ATR and its activator Rad24RAD17 during meiotic recombination.PLoS genetics · 2024Article
- The Dmc1 recombinase physically interacts with and promotes the meiotic crossover functions of the Mlh1-Mlh3 endonuclease.Genetics · 2024Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Crossing over between homologs is initiated in meiotic prophase by the formation of DNA double-strand breaks that occur throughout the genome. In the major interference-responsive crossover pathway in baker's yeast, these breaks are resected to form 3' single-strand tails that participate in a homology search, ultimately forming double Holliday junctions (dHJs) that primarily include both homologs. These dHJs are resolved by endonuclease activity to form exclusively crossovers, which are critical for proper homolog segregation in Meiosis I. Recent genetic, biochemical, and molecular studies in yeast are consistent with the hypothesis of Mlh1-Mlh3 DNA mismatch repair complex acting as the major endonuclease activity that resolves dHJs into crossovers. However, the mechanism by which the Mlh1-Mlh3 endonuclease is activated is unknown. Here, we provide evidence that Mlh1-Mlh3 does not behave like a structure-specific endonuclease but forms polymers required to generate nicks in DNA. This conclusion is supported by DNA binding studies performed with different-sized substrates that contain or lack polymerization barriers and endonuclease assays performed with varying ratios of endonuclease-deficient and endonuclease-proficient Mlh1-Mlh3. In addition, Mlh1-Mlh3 can generate religatable double-strand breaks and form an active nucleoprotein complex that can nick DNA substrates in trans. Together these observations argue that Mlh1-Mlh3 may not act like a canonical, RuvC-like Holliday junction resolvase and support a novel model in which Mlh1-Mlh3 is loaded onto DNA to form an activated polymer that cleaves DNA.
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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.