ArticleNature genetics2021
Increased somatic mutation burdens in normal human cells due to defective DNA polymerases.
Article in Nature genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.
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Who cites it
119 citing papers in PubMed, 172 citations in OpenAlex.
- Dynamics of mutators of arbitrary dominance in humans.bioRxiv : the preprint server for biology · 2026Article
- Article
- Integration of multi-omics data uncovers novel germline susceptibility candidates in early-onset colorectal cancer.European journal of human genetics : EJHG · 2026Article
- Motif-centered analyses reveal universal and tissue-specific mutagenic mechanisms operating in the human body.NAR cancer · 2026Article
- Identification and validation of a previously missed mutational signature in colorectal cancer.Nature communications · 2026Article
- Article
- What sets the mutation rate of a cell type in an animal species?PLoS biology · 2026Article
- The aging genome exhibits organized vulnerability to somatic mutations.bioRxiv : the preprint server for biology · 2026Article
- Motif-Centered Analyses Reveal Universal and Tissue-Specific Mutagenic Mechanisms Operating in the Human Body.bioRxiv : the preprint server for biology · 2026Article
- Organelle resilience as a comparative blueprint for longevity.EMBO molecular medicine · 2026Review
- Somatic mutations and clonal evolution in normal tissues and cancer development.Experimental & molecular medicine · 2026Review
- Application of chromosomal microarray analysis and trio whole-exome sequencing in first-trimester prenatal diagnosis for high-risk pregnancies.BMC pregnancy and childbirth · 2026Article
- From molecular damage to regulatory constraint: epigenetic and metabolic limits of cellular plasticity in aging.Frontiers in aging · 2026Review
- Selection, Comparative Genomics, and Potential Probiotic Features of Escherichia coli 5C, a pks-Negative Strain Isolated from Healthy Infant Donor Feces.Probiotics and antimicrobial proteins · 2026Article
- What sets the mutation rate of a cell type in an animal species?bioRxiv : the preprint server for biology · 2025Article
- Mathematical Modeling Quantifies "Just-Right" APC Inactivation for Colorectal Cancer Initiation.Cancer research · 2025Article
- Reconstructing the lifelong history of cells and tissues via somatic mutation analysis.Cellular and molecular life sciences : CMLS · 2025Review
- The germline POLD1 c.1420 C > A (p.Leu474Ile) variant segregates with endometrial cancer, colorectal cancer and colonic polyps demonstrating hypermutation and defective POLD1 mutational signatures.Familial cancer · 2025Article
- The evolution of cancer and ageing: a history of constraint.Nature reviews. Cancer · 2025Review
- Increased nucleotide metabolism alleviates Alzheimer's disease pathology.Cell death & disease · 2025Article
59 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 3 countries.
Funding
Abstract
Mutation accumulation in somatic cells contributes to cancer development and is proposed as a cause of aging. DNA polymerases Pol ε and Pol δ replicate DNA during cell division. However, in some cancers, defective proofreading due to acquired POLE/POLD1 exonuclease domain mutations causes markedly elevated somatic mutation burdens with distinctive mutational signatures. Germline POLE/POLD1 mutations cause familial cancer predisposition. Here, we sequenced normal tissue and tumor DNA from individuals with germline POLE/POLD1 mutations. Increased mutation burdens with characteristic mutational signatures were found in normal adult somatic cell types, during early embryogenesis and in sperm. Thus human physiology can tolerate ubiquitously elevated mutation burdens. Except for increased cancer risk, individuals with germline POLE/POLD1 mutations do not exhibit overt features of premature aging. These results do not support a model in which all features of aging are attributable to widespread cell malfunction directly resulting from somatic mutation burdens accrued during life.
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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.