ArticleGenetics2007
Functional characterization of pathogenic human MSH2 missense mutations in Saccharomyces cerevisiae.
Article in Genetics, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
54 citing papers in PubMed, 93 citations in OpenAlex.
- Lynch Syndrome: An Update of Underlying Molecular Mechanisms, Phenotypes and Methods to Classify Variants of Uncertain Significance.Biomedicines · 2026Review
- An accurate cellular assay to determine pathogenicity of coding and noncoding variants in Lynch syndrome genes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Signification and Application of Mutator and Antimutator Phenotype-Induced Genetic Variations in Evolutionary Adaptation and Cancer Therapeutics.Journal of microbiology (Seoul, Korea) · 2023Review
- Whole exome sequencing identifies MAP3K1, MSH2, and MLH1 as potential cancer-predisposing genes in familial early-onset colorectal cancer.The Kaohsiung journal of medical sciences · 2023Article
- The [PSIMolecular biology of the cell · 2022Article
- Article
- Review
- Do non-pathogenic variants of DNA mismatch repair genes modify neurofibroma load in neurofibromatosis type 1?Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2022Review
- Multiplexing mutation rate assessment: determining pathogenicity of Msh2 variants in Saccharomyces cerevisiae.Genetics · 2021Article
- Setting molecular traps in yeast for identification of anticancer drug targets.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Yeast-based screening of cancer mutations in the DNA damage response protein Mre11 demonstrates importance of conserved capping domain residues.Molecular biology reports · 2021Article
- MutSα mismatch repair protein stability is governed by subunit interaction, acetylation, and ubiquitination.G3 (Bethesda, Md.) · 2021Article
- Multiplexed assays reveal effects of missense variants in MSH2 and cancer predisposition.PLoS genetics · 2021Article
- Yeast-based assays for the functional characterization of cancer-associated variants of human DNA repair genes.Microbial cell (Graz, Austria) · 2020Review
- New Pathogenic Germline Variants in Very Early Onset and Familial Colorectal Cancer Patients.Frontiers in genetics · 2020Article
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- Article
- Functional interrogation of Lynch syndrome-associated MSH2 missense variants via CRISPR-Cas9 gene editing in human embryonic stem cells.Human mutation · 2019Article
- Article
- The Mutator Phenotype: Adapting Microbial Evolution to Cancer Biology.Frontiers in genetics · 2019Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Hereditary nonpolyposis colorectal cancer (HNPCC) is associated with defects in DNA mismatch repair. Mutations in either hMSH2 or hMLH1 underlie the majority of HNPCC cases. Approximately 25% of annotated hMSH2 disease alleles are missense mutations, resulting in a single change out of 934 amino acids. We engineered 54 missense mutations in the cognate positions in yeast MSH2 and tested for function. Of the human alleles, 55% conferred strong defects, 8% displayed intermediate defects, and 38% showed no defects in mismatch repair assays. Fifty percent of the defective alleles resulted in decreased steady-state levels of the variant Msh2 protein, and 49% of the Msh2 variants lost crucial protein-protein interactions. Finally, nine positions are predicted to influence the mismatch recognition complex ATPase activity. In summary, the missense mutations leading to loss of mismatch repair defined important structure-function relationships and the molecular analysis revealed the nature of the deficiency for Msh2 variants expressed in the tumors. Of medical relevance are 15 human alleles annotated as pathogenic in public databases that conferred no obvious defects in mismatch repair assays. This analysis underscores the importance of functional characterization of missense alleles to ensure that they are the causative factor for disease.
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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.