ArticleGenome biology2018
Reduced intrinsic DNA curvature leads to increased mutation rate.
Article in Genome biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
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- The Causes for Genomic Instability and How to Try and Reduce Them Through Rational Design of Synthetic DNA.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Structural underpinnings of mutation rate variations in the human genome.Nucleic acids research · 2023Article
- Is the Mutation Rate Lower in Genomic Regions of Stronger Selective Constraints?Molecular biology and evolution · 2022Article
- Spontaneous mutation rate estimates for the principal malaria vectors Anopheles coluzzii and Anopheles stephensi.Scientific reports · 2022Article
- Engineering neoantigen vaccines to improve cancer personalized immunotherapy.International journal of biological sciences · 2022Review
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- Non-Darwinian Molecular Biology.Frontiers in genetics · 2022Review
- Host-specific asymmetric accumulation of mutation types reveals that the origin of SARS-CoV-2 is consistent with a natural process.Innovation (Cambridge (Mass.)) · 2021Article
- A rapidly reversible mutation generates subclonal genetic diversity and unstable drug resistance.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- A mutational hotspot that determines highly repeatable evolution can be built and broken by silent genetic changes.Nature communications · 2021Article
- Intrinsic DNA topology as a prioritization metric in genomic fine-mapping studies.Nucleic acids research · 2020Article
- Genome-Wide Analyses Revealed Remarkable Heterogeneity in Pathogenicity Determinants, Antimicrobial Compounds, and CRISPR-Cas Systems of Complex Phytopathogenic GenusPathogens (Basel, Switzerland) · 2019Article
- Evolution of Genomic Base Composition: From Single Cell Microbes to Multicellular Animals.Computational and structural biotechnology journal · 2019Review
- Nucleosome positions establish an extended mutation signature in melanoma.PLoS genetics · 2018Article
- Reduced intrinsic DNA curvature leads to increased mutation rate.Genome biology · 2018Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundMutation rates vary across the genome. Many trans factors that influence mutation rates have been identified, as have specific sequence motifs at the 1-7-bp scale, but cis elements remain poorly characterized. The lack of understanding regarding why different sequences have different mutation rates hampers our ability to identify positive selection in evolution and to identify driver mutations in tumorigenesis.
resultsHere, we use a combination of synthetic genes and sequences of thousands of isolated yeast colonies to show that intrinsic DNA curvature is a major cis determinant of mutation rate. Mutation rate negatively correlates with DNA curvature within genes, and a 10% decrease in curvature results in a 70% increase in mutation rate. Consistently, both yeast and humans accumulate mutations in regions with small curvature. We further show that this effect is due to differences in the intrinsic mutation rate, likely due to differences in mutagen sensitivity and not due to differences in the local activity of DNA repair.
conclusionsOur study establishes a framework for understanding the cis properties of DNA sequence in modulating the local mutation rate and identifies a novel causal source of non-uniform mutation rates across the genome.
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