ArticleProceedings of the National Academy of Sciences of the United States of America2002
Mbd4 inactivation increases Cright-arrowT transition mutations and promotes gastrointestinal tumor formation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 175 citations in OpenAlex.
- Gene regulatory mechanisms downstream of DNA methylation.Nature reviews. Genetics · 2026Review
- Mbd4 and MutSα protect cells from spontaneous deamination of 5-methylcytosine.Nucleic acids research · 2026Article
- The Influence of CG sites on dynamic DNA sequence mutagenesis in the genomic evolution of mammalian lifespan.Nucleic acids research · 2025Article
- Structure of a DNA Glycosylase Bound to a Nicked T:G Mismatch-Containing DNA.Molecules (Basel, Switzerland) · 2025Article
- Base-excision repair pathway shapes 5-methylcytosine deamination signatures in pan-cancer genomes.Nature communications · 2024Article
- Prognostic Significance ofPhenomics (Cham, Switzerland) · 2024Article
- Single Nucleotide Polymorphisms (SNPs) in the Shadows: Uncovering their Function in Non-Coding Region of Esophageal Cancer.Current pharmaceutical biotechnology · 2024Review
- A naturally occurring variant ofGenome research · 2023Article
- MBD4 loss results in global reactivation of promoters and retroelements with low methylated CpG density.Journal of experimental & clinical cancer research : CR · 2023Article
- From Chaos to Opportunity: Decoding Cancer Heterogeneity for Enhanced Treatment Strategies.Biology · 2023Review
- Targeted DNA Demethylation: Vectors, Effectors and Perspectives.Biomedicines · 2023Review
- Heterozygous loss of Zbtb38 leads to early embryonic lethality via the suppression of Nanog and Sox2 expression.Cell proliferation · 2022Article
- Proteins That Read DNA Methylation.Advances in experimental medicine and biology · 2022Article
- Active DNA demethylation-The epigenetic gatekeeper of development, immunity, and cancer.Advanced genetics (Hoboken, N.J.) · 2021Review
- Role of mismatch repair in aging.International journal of biological sciences · 2021Review
- The complex relationship between MITF and the immune system: a Melanoma ImmunoTherapy (response) Factor?Molecular cancer · 2020Review
- Genetic variants of the peroxisome proliferator-activated receptor (PPAR) signaling pathway genes and risk of pancreatic cancer.Molecular carcinogenesis · 2020Article
- Investigating Tumor Heterogeneity in Mouse Models.Annual review of cancer biology · 2020Article
- Multi-Omics Analysis to Characterize Cigarette Smoke Induced Molecular Alterations in Esophageal Cells.Frontiers in oncology · 2020Article
- Base Excision Repair in the Immune System: Small DNA Lesions With Big Consequences.Frontiers in immunology · 2020Review
22 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Mbd4 (methyl-CpG binding domain 4) is a novel mammalian repair enzyme that has been implicated biochemically in the repair of mismatched G-T residues at methylated CpG sites. In addition, the human protein has been shown to interact with the DNA mismatch repair protein MLH1. To clarify the role of Mbd4 in DNA repair in vivo and to examine the impact of Mbd4 inactivation on gastrointestinal (GI) tumorigenesis, we introduced a null mutation into the murine Mbd4 gene by gene targeting. Heterozygous and homozygous Mbd4 mutant mice develop normally and do not show increased cancer susceptibility or reduced survival. Although Mbd4 inactivation did not increase microsatellite instability (MSI) in the mouse genome, it did result in a 2- to 3-fold increase in C-->T transition mutations at CpG sequences in splenocytes and epithelial cells of the small intestinal mucosa. The combination of Mbd4 deficiency with a germ line mutation in the adenomatous polyposis coli (Apc) gene increased the tumor number in the GI tract and accelerated tumor progression. The change in the GI cancer phenotype was associated with an increase in somatic C-->T mutations at CpG sites within the coding region of the wild-type Apc allele. These studies indicate that, although inactivation of Mbd4 does not by itself cause cancer predisposition in mice, it can alter the mutation spectrum in cancer cells and modify the cancer predisposition phenotype.
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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.