ArticleJournal of molecular biology2012
The unstructured linker arms of Mlh1-Pms1 are important for interactions with DNA during mismatch repair.
Article in Journal of molecular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 39 citations in OpenAlex.
- The marsupial imprinted gene MLH1 has retrocopies in three marsupial families.Epigenetics & chromatin · 2026Article
- The GHKL ATPase Family as a Paradigm for MutL Homolog Function in DNA Mismatch Repair.International journal of molecular sciences · 2025Review
- Mlh1-Pms1 couples ATP-driven DNA compaction with nick-dependent endonuclease activation.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
- Functions of PMS2 and MLH1 important for regulation of divergent repeat-mediated deletions.DNA repair · 2025Article
- Functions of PMS2 and MLH1 important for regulation of divergent repeat-mediated deletions.bioRxiv : the preprint server for biology · 2024Article
- The Dmc1 recombinase physically interacts with and promotes the meiotic crossover functions of the Mlh1-Mlh3 endonuclease.Genetics · 2024Article
- The Mlh1-Pms1 endonuclease uses ATP to preserve DNA discontinuities as strand discrimination signals to facilitate mismatch repair.bioRxiv : the preprint server for biology · 2024Article
- The Dmc1 recombinase physically interacts with and promotes the meiotic crossover functions of the Mlh1-Mlh3 endonuclease.bioRxiv : the preprint server for biology · 2023Article
- Gene expression of non-homologous end-joining pathways in the prognosis of ovarian cancer.iScience · 2023Article
- Insights into DNA cleavage by MutL homologs from analysis of conserved motifs in eukaryotic Mlh1.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Article
- Key role of phosphorylation sites in ATPase domain and Linker region of MLH1 for DNA binding and functionality of MutLα.Scientific reports · 2023Article
- A conserved motif in the disordered linker of human MLH1 is vital for DNA mismatch repair and its function is diminished by a cancer family mutation.Nucleic acids research · 2023Article
- The unstructured linker of Mlh1 contains a motif required for endonuclease function which is mutated in cancers.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Handcuffing intrinsically disordered regions in Mlh1-Pms1 disrupts mismatch repair.Nucleic acids research · 2021Article
- Expanded roles for the MutL family of DNA mismatch repair proteins.Yeast (Chichester, England) · 2021Review
- The unstructured linker arms of MutL enable GATC site incision beyond roadblocks during initiation of DNA mismatch repair.Nucleic acids research · 2019Article
- Intrinsically disordered regions regulate both catalytic and non-catalytic activities of the MutLα mismatch repair complex.Nucleic acids research · 2019Article
- mlh3 mutations in baker's yeast alter meiotic recombination outcomes by increasing noncrossover events genome-wide.PLoS genetics · 2017Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
DNA mismatch repair (MMR) models have proposed that MSH (MutS homolog) proteins identify DNA polymerase errors while interacting with the DNA replication fork. MLH (MutL homolog) proteins (primarily Mlh1-Pms1 in baker's yeast) then survey the genome for lesion-bound MSH proteins. The resulting MSH-MLH complex formed at a DNA lesion initiates downstream steps in repair. MLH proteins act as dimers and contain long (20-30 nm) unstructured arms that connect two terminal globular domains. These arms can vary between 100 and 300 amino acids in length, are highly divergent between organisms, and are resistant to amino acid substitutions. To test the roles of the linker arms in MMR, we engineered a protease cleavage site into the Mlh1 linker arm domain of baker's yeast Mlh1-Pms1. Cleavage of the Mlh1 linker arm in vitro resulted in a defect in Mlh1-Pms1 DNA binding activity, and in vivo proteolytic cleavage resulted in a complete defect in MMR. We then generated a series of truncation mutants bearing Mlh1 and Pms1 linker arms of varying lengths. This work revealed that MMR is greatly compromised when portions of the Mlh1 linker are removed, whereas repair is less sensitive to truncation of the Pms1 linker arm. Purified complexes containing truncations in Mlh1 and Pms1 linker arms were analyzed and found to have differential defects in DNA binding that also correlated with the ability to form a ternary complex with Msh2-Msh6 and mismatch DNA. These observations are consistent with the unstructured linker domains of MLH proteins providing distinct interactions with DNA during MMR.
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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.