ArticleMolecular and cellular biology1999
Mutator phenotypes conferred by MLH1 overexpression and by heterozygosity for mlh1 mutations.
Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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106 citing papers in PubMed, 189 citations in OpenAlex.
- The marsupial imprinted gene MLH1 has retrocopies in three marsupial families.Epigenetics & chromatin · 2026Article
- Lynch Syndrome: An Update of Underlying Molecular Mechanisms, Phenotypes and Methods to Classify Variants of Uncertain Significance.Biomedicines · 2026Review
- A thumb-domain insertion balances processivity and fidelity in DNA polymerase ε.Nucleic acids research · 2026Article
- Evidence that MutSβ repairs indels generated by mispair initiated template slippage.DNA repair · 2026Article
- 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
- Vulnerable Nucleotide Pools and Genomic Instability in Yeast Strains with Deletion of theInternational journal of molecular sciences · 2025Article
- Functions of PMS2 and MLH1 important for regulation of divergent repeat-mediated deletions.DNA repair · 2025Article
- High fidelity DNA ligation prevents single base insertions in the yeast genome.Nature communications · 2024Article
- Functions of PMS2 and MLH1 important for regulation of divergent repeat-mediated deletions.bioRxiv : the preprint server for biology · 2024Article
- Sustained inactivation of the Polycomb PRC1 complex induces DNA repair defects and genomic instability in epigenetic tumors.Histochemistry and cell biology · 2024Article
- Enhanced eMAGE applied to identify genetic factors of nuclear hormone receptor dysfunction via combinatorial gene editing.Nature communications · 2024Article
- Sustained inactivation of the Polycomb PRC1 complex induces DNA repair defects and genomic instability in epigenetic tumors.Research square · 2024Article
- Elevated MSH2 MSH3 expression interferes with DNA metabolism in vivo.Nucleic acids research · 2023Article
- Polymorphism ofInternational journal of molecular sciences · 2023Article
- OTUB1-mediated inhibition of ubiquitination: a growing list of effectors, multiplex mechanisms, and versatile functions.Frontiers in molecular biosciences · 2023Review
- Molecular basis for processing of topoisomerase 1-triggered DNA damage by Apn2/APE2.Cell reports · 2022Article
- Enhanced polymerase activity permits efficient synthesis by cancer-associated DNA polymerase ϵ variants at low dNTP levels.Nucleic acids research · 2022Article
- The nuclease activity of DNA2 promotes exonuclease 1-independent mismatch repair.The Journal of biological chemistry · 2022Article
- Mismatch Repair Proteins in Oropharyngeal Squamous Cell Carcinoma: A Retrospective Observational Study.Head and neck pathology · 2021Observational
46 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Loss of DNA mismatch repair due to mutation or diminished expression of the MLH1 gene is associated with genome instability and cancer. In this study, we used a yeast model system to examine three circumstances relevant to modulation of MLH1 function. First, overexpression of wild-type MLH1 was found to cause a strong elevation of mutation rates at three different loci, similar to the mutator effect of MLH1 gene inactivation. Second, haploid yeast strains with any of six mlh1 missense mutations that mimic germ line mutations found in human cancer patients displayed a strong mutator phenotype consistent with loss of mismatch repair function. Five of these mutations affect amino acids that are homologous to residues suggested by recent crystal structure and biochemical analysis of Escherichia coli MutL to participate in ATP binding and hydrolysis. Finally, using a highly sensitive reporter gene, we detected a mutator phenotype of diploid yeast strains that are heterozygous for mlh1 mutations. Evidence suggesting that this mutator effect results not from reduced mismatch repair in the MLH1/mlh1 cells but rather from loss of the wild-type MLH1 allele in a fraction of cells is presented. Exposure to bleomycin or to UV irradiation strongly enhanced mutagenesis in the heterozygous strain but had little effect on the mutation rate in the wild-type strain. This damage-induced hypermutability may be relevant to cancer in humans with germ line mutations in only one MLH1 allele.
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