ArticleThe EMBO journal2003
Methylation-induced G(2)/M arrest requires a full complement of the mismatch repair protein hMLH1.
Article in The EMBO journal, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.
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Who cites it
80 citing papers in PubMed, 1 synthesis or guideline pooled it, 188 citations in OpenAlex.
- Association between MutL homolog 1 polymorphisms and the risk of colorectal cancer: a meta-analysis.Journal of cancer research and clinical oncology · 2015Pooled it
- 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
- Genetic Variation ofInternational journal of dentistry · 2026Article
- Nonrepair functions of DNA mismatch repair proteins: new avenues for precision oncology.Trends in cancer · 2025Review
- Therapeutic validation of MMR-associated genetic modifiers in a human ex vivo model of Huntington disease.American journal of human genetics · 2024Article
- Review
- Multiplex single-cell chemical genomics reveals the kinase dependence of the response to targeted therapy.Cell genomics · 2024Article
- Tumor-independent Detection of Inherited Mismatch Repair Deficiency for the Diagnosis of Lynch Syndrome with High Specificity and Sensitivity.Cancer research communications · 2023Article
- A calibrated cell-based functional assay to aid classification of MLH1 DNA mismatch repair gene variants.Human mutation · 2022Article
- Role of EXO1 nuclease activity in genome maintenance, the immune response and tumor suppression in Exo1D173A mice.Nucleic acids research · 2022Article
- Prime editing efficiency and fidelity are enhanced in the absence of mismatch repair.Nature communications · 2022Article
- Inhibition of ABL1 by tyrosine kinase inhibitors leads to a downregulation of MLH1 by Hsp70-mediated lysosomal protein degradation.Frontiers in genetics · 2022Article
- Immunoprofiles and DNA Methylation of Inflammatory Marker Genes in Ulcerative Colitis-Associated Colorectal Tumorigenesis.Biomolecules · 2021Article
- FANCD2-Associated Nuclease 1 Partially Compensates for the Lack of Exonuclease 1 in Mismatch Repair.Molecular and cellular biology · 2021Article
- Genetic evidence for the involvement of mismatch repair proteins, PMS2 and MLH3, in a late step of homologous recombination.The Journal of biological chemistry · 2020Article
- Epigenetic preconditioning with decitabine sensitizes glioblastoma to temozolomide via induction of MLH1.Journal of neuro-oncology · 2020Article
- Does breast carcinoma belong to the Lynch syndrome tumor spectrum? - Somatic mutational profiles vs. ovarian and colorectal carcinomas.Oncotarget · 2020Article
- DNA methylation changes and somatic mutations as tumorigenic events in Lynch syndrome-associated adenomas retaining mismatch repair protein expression.EBioMedicine · 2019Article
- The mutagen and carcinogen cadmium is a high-affinity inhibitor of the zinc-dependent MutLα endonuclease.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Mlh1 deficiency in normal mouse colon mucosa associates with chromosomally unstable colon cancer.Carcinogenesis · 2018Article
20 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
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mismatch repair (MMR) gene hMLH1 is mutated in approximately 50% of hereditary non-polyposis colon cancers and transcriptionally silenced in approximately 25% of sporadic tumours of the right colon. Cells lacking hMLH1 display microsatellite instability and resistance to killing by methylating agents. In an attempt to study the phenotypic effects of hMLH1 downregulation in greater detail, we designed an isogenic system, in which hMLH1 expression is regulated by doxycycline. We now report that human embryonic kidney 293T cells expressing high amounts of hMLH1 were MMR-proficient and arrested at the G(2)/M cell cycle checkpoint following treatment with the DNA methylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), while cells not expressing hMLH1 displayed a MMR defect and failed to arrest upon MNNG treatment. Interestingly, MMR proficiency was restored even at low hMLH1 concentrations, while checkpoint activation required a full complement of hMLH1. In the MMR-proficient cells, activation of the MNNG-induced G(2)/M checkpoint was accompanied by phosphorylation of p53, but the cell death pathway was p53 independent, as the latter polypeptide is functionally inactivated in these cells by SV40 large T antigen.
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