ArticleScience advances2021
Deficiency of replication-independent DNA mismatch repair drives a 5-methylcytosine deamination mutational signature in cancer.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Human PMS1-dependent non-canonical mismatch repair engages with MBD4 to repair methylated CpG deamination.Nucleic acids research · 2026Article
- Germline haploinsufficiency of MUTYH causes mutational signature SBS18 in multiple tumour types and specifically raises colorectal cancer risk.NPJ precision oncology · 2026Article
- Molecular characterization of the A52 murine hepatocellular carcinoma cell line.Animal models and experimental medicine · 2026Article
- Mbd4 and MutSα protect cells from spontaneous deamination of 5-methylcytosine.Nucleic acids research · 2026Article
- Patterns of hypermutation shape tumorigenesis and immunotherapy response in mismatch-repair-deficient glioma.Nature genetics · 2026Article
- Genomic characterization of host gene alterations in Theileria annulata-transformed leukocytes.Communications biology · 2025Article
- Proteomic Analysis Uncovers Enhanced Inflammatory Phenotype and Distinct Metabolic Changes in IDH1 Mutant Glioma Cells.International journal of molecular sciences · 2025Article
- Replication-associated mechanisms contribute to an increased CpG > TpG mutation burden in mismatch repair-deficient cancers.Genome medicine · 2025Article
- Unraveling mutagenic processes influencing the tumor mutational patterns of individuals with constitutional mismatch repair deficiency.Nature communications · 2025Article
- A review on trends in development and translation of omics signatures in cancer.Computational and structural biotechnology journal · 2024Review
- Chemoproteogenomic stratification of the missense variant cysteinome.Nature communications · 2024Article
- Somatic CpG hypermutation is associated with mismatch repair deficiency in cancer.Molecular systems biology · 2024Article
- Mutational Signatures in Colorectal Cancer: Translational Insights, Clinical Applications, and Limitations.Cancers · 2024Review
- Alcohol and colorectal cancer risk, subclassified by mutational signatures of DNA mismatch repair deficiency.Journal of the National Cancer Institute · 2024Article
- Genetic gear switches drive cancer immune evasion.Nature genetics · 2024Article
- Homopolymer switches mediate adaptive mutability in mismatch repair-deficient colorectal cancer.Nature genetics · 2024Article
- The clock-like accumulation of germline and somatic mutations can arise from the interplay of DNA damage and repair.PLoS biology · 2024Article
- H3K4me1 recruits DNA repair proteins in plants.The Plant cell · 2024Article
- Mutational signatures of colorectal cancers according to distinct computational workflows.Briefings in bioinformatics · 2024Article
- Novel insights into tumorigenesis revealed by molecular analysis of Lynch syndrome cases with multiple colorectal tumors.Frontiers in oncology · 2024Article
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple mutational signatures have been associated with DNA mismatch repair (MMR)–deficient cancers, but the mechanisms underlying their origin remain unclear. Here, using mutation data from cancer genomes, we identify a previously unknown function of MMR that is able to protect genomes from 5-methylcytosine (5mC) deamination–induced somatic mutations in a replication-independent manner. Cancers with deficiency of MMR proteins MSH2/MSH6 (MutSα) exhibit mutational signature contributions distinct from those that are deficient in MLH1/PMS2 (MutLα). This disparity arises from unrepaired 5mC deamination–induced mismatches rather than replicative DNA polymerase errors. In cancers with biallelic loss of MBD4 DNA glycosylase, repair of 5mC deamination damage is strongly associated with H3K36me3 chromatin, implicating MutSα as the essential factor in its repair. We thus uncover a noncanonical role of MMR in the protection against 5mC deamination–induced mutation in human cancers.
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