1. Loops are geometric catalysts for DNA integration.
- Author
-
Battaglia C and Michieletto D
- Subjects
- Chromatin chemistry, Chromatin genetics, Chromatin metabolism, DNA Transposable Elements genetics, DNA, Viral genetics, DNA, Viral chemistry, Mutagenesis, Insertional, Molecular Dynamics Simulation, Nucleic Acid Conformation, DNA chemistry, DNA genetics, Nucleosomes chemistry, Nucleosomes genetics, Nucleosomes metabolism
- Abstract
The insertion of DNA elements within genomes underpins both genetic diversity and disease when unregulated. Most of DNA insertions are not random and the physical mechanisms underlying the integration site selection are poorly understood. Here, we perform Molecular Dynamics simulations to study the insertion of DNA elements, such as viral DNA or transposons, into naked DNA or chromatin substrates. More specifically, we explore the role of loops within the polymeric substrate and discover that they act as 'geometric catalysts' for DNA integration by reducing the energy barrier for substrate deformation. Additionally, we discover that the 1D pattern and 3D conformation of loops have a marked effect on the distribution of integration sites. Finally, we show that loops may compete with nucleosomes to attract DNA integrations. These results may be tested in vitro and they may help to understand patterns of DNA insertions with implications in genome evolution and engineering., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2024
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