ArticleProceedings of the National Academy of Sciences of the United States of America2016
Inevitability and containment of replication errors for eukaryotic genome lengths spanning megabase to gigabase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
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- Nanopore sequencing reveals that DNA replication compartmentalisation dictates genome stability and instability in Trypanosoma brucei.Nature communications · 2025Article
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- DDK: The Outsourced Kinase of Chromosome Maintenance.Biology · 2022Review
- Hydroxyurea-The Good, the Bad and the Ugly.Genes · 2021Review
- CUL2EMBO reports · 2021Article
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- Read, Write, Adapt: Challenges and Opportunities during Kinetoplastid Genome Replication.Trends in genetics : TIG · 2021Review
- RAD52: Paradigm of Synthetic Lethality and New Developments.Frontiers in genetics · 2021Review
- Limiting homologous recombination at stalled replication forks is essential for cell viability: DNA2 to the rescue.Current genetics · 2020Review
- Under-Replicated DNA: The Byproduct of Large Genomes?Cancers · 2020Review
- Genome duplication ineLife · 2020Article
- Transcription activity contributes to the firing of non-constitutive origins in African trypanosomes helping to maintain robustness in S-phase duration.Scientific reports · 2019Article
- Putting the brakes on the cell cycle: mechanisms of cellular growth arrest.Current opinion in cell biology · 2019Review
- TRAIP drives replisome disassembly and mitotic DNA repair synthesis at sites of incomplete DNA replication.eLife · 2019Article
- 53BP1 nuclear bodies enforce replication timing at under-replicated DNA to limit heritable DNA damage.Nature cell biology · 2019Article
- Review
- Rapid high-resolution measurement of DNA replication timing by droplet digital PCR.Nucleic acids research · 2018Article
- Emerging roles of CST in maintaining genome stability and human disease.Frontiers in bioscience (Landmark edition) · 2018Review
- Thymic involution and rising disease incidence with age.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The replication of DNA is initiated at particular sites on the genome called replication origins (ROs). Understanding the constraints that regulate the distribution of ROs across different organisms is fundamental for quantifying the degree of replication errors and their downstream consequences. Using a simple probabilistic model, we generate a set of predictions on the extreme sensitivity of error rates to the distribution of ROs, and how this distribution must therefore be tuned for genomes of vastly different sizes. As genome size changes from megabases to gigabases, we predict that regularity of RO spacing is lost, that large gaps between ROs dominate error rates but are heavily constrained by the mean stalling distance of replication forks, and that, for genomes spanning ∼100 megabases to ∼10 gigabases, errors become increasingly inevitable but their number remains very small (three or less). Our theory predicts that the number of errors becomes significantly higher for genome sizes greater than ∼10 gigabases. We test these predictions against datasets in yeast, Arabidopsis, Drosophila, and human, and also through direct experimentation on two different human cell lines. Agreement of theoretical predictions with experiment and datasets is found in all cases, resulting in a picture of great simplicity, whereby the density and positioning of ROs explain the replication error rates for the entire range of eukaryotes for which data are available. The theory highlights three domains of error rates: negligible (yeast), tolerable (metazoan), and high (some plants), with the human genome at the extreme end of the middle domain.
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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.