ArticleScience (New York, N.Y.)2016
Stochastic activation of a DNA damage response causes cell-to-cell mutation rate variation.
Article in Science (New York, N.Y.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
What it found
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The trial behind it
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
86 citing papers in PubMed, 169 citations in OpenAlex.
- Heterogeneity in microbial antibiotic responses: genetic basis and within-host evolution.Trends in genetics : TIG · 2026Review
- Growth rate-dependent mutations and phenotypic switching facilitate rapid adaptation.NPJ systems biology and applications · 2026Article
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- Induced tolerance to UV stress drives survival heterogeneity in isogenic E. coli cell populations.Scientific reports · 2026Article
- AI-based methods for the assessment of DNA damage and repair mechanisms.Frontiers in systems biology · 2026Review
- Toward single-cell control: noise-robust perfect adaptation in biomolecular systems.Nature communications · 2025Article
- Feedforward miR-181d degradation modulates population variance of methyl-guanine methyl transferase and temozolomide resistance.Cell reports · 2025Article
- A transient mutational burst occurs during yeast colony development.Molecular systems biology · 2025Article
- Article
- In vivo single-molecule imaging of RecB reveals efficient repair of DNA damage in Escherichia coli.Nucleic acids research · 2025Article
- Induced tolerance to UV stress drives survival heterogeneity in isogenicbioRxiv : the preprint server for biology · 2025Article
- Quantifying cell fate change under different stochastic gene activation frameworks.Quantitative biology (Beijing, China) · 2025Article
- Harnessing microbial heterogeneity for improved biosynthesis fueled by synthetic biology.Synthetic and systems biotechnology · 2025Review
- Robust Quantification of Live-Cell Single-Molecule Tracking Data for Fluorophores with Different Photophysical Properties.The journal of physical chemistry. B · 2024Article
- Regulatory properties of transcription factors with diverse mechanistic function.PLoS computational biology · 2024Article
- Estimating mutation rates under heterogeneous stress responses.PLoS computational biology · 2024Article
- Widespread prevalence of a methylation-dependent switch to activate an essential DNA damage response in bacteria.PLoS biology · 2024Article
- Genomic and metabolic instability during long-term fermentation of an industrialFrontiers in bioengineering and biotechnology · 2024Article
- The divergence of mutation rates and spectra across the Tree of Life.EMBO reports · 2023Review
- Protein secretion zones during overexpression of amylase within the Gram-positive cell wall.BMC biology · 2023Article
26 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
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Cells rely on the precise action of proteins that detect and repair DNA damage. However, gene expression noise causes fluctuations in protein abundances that may compromise repair. For the Ada protein in Escherichia coli, which induces its own expression upon repairing DNA alkylation damage, we found that undamaged cells on average produce one Ada molecule per generation. Because production is stochastic, many cells have no Ada molecules and cannot induce the damage response until the first expression event occurs, which sometimes delays the response for generations. This creates a subpopulation of cells with increased mutation rates. Nongenetic variation in protein abundances thus leads to genetic heterogeneity in the population. Our results further suggest that cells balance reliable repair against toxic side effects of abundant DNA repair proteins.
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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.