Loops are Geometric Catalysts for DNA Integration

TL;DR

This study uses Molecular Dynamics simulations to reveal that DNA loops act as geometric catalysts influencing the site selection of DNA integration, with implications for genome evolution and gene therapy.

Contribution

It uncovers the role of DNA loops as geometric catalysts in integration site selection, a novel insight into the physical mechanisms of DNA insertion.

Findings

Loops promote DNA integration at specific sites.

Clustering of loops influences integration distribution.

Loops compete with nucleosomes for DNA integration sites.

Abstract

The insertion of HIV and other DNA elements within genomes underpins both genetic diversity and disease when unregulated. Most of these insertions are not random and occupy specific positions within the genome but 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 HIV viral DNA or transposons, into naked DNA or chromatin substrate. More specifically, we explore the role of loops in the DNA substrate and discover that they act as "geometric catalysts" for DNA integration. Additionally, we discover that the 1D and 3D clustering of loops affects the distribution of integration sites. Finally, we show that loops may compete with nucleosomes at attracting 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 gene therapy.