When it comes to packaging large amounts of information into tiny volumes, biology and physics often buddy up to reach creative solutions. The problem is even more complex with DNA, as the compacted information must also remain accessible to the proteins in charge of transcription. Understanding the way DNA is packaged in a cell therefore provides crucial insights into how gene expression is regulated.
Using a combination of high resolution imaging techniques (Atomic Force Microscopy, AFM), theoretical modelling and molecular dynamics calculations, a multidisciplinary team of researchers, including Fabrizio Benedetti from SIB's Vital-IT group, observed for the first time a brand new DNA folding structure they coined ‘hyperplectoneme’.
Anyone who has ever played with a rubber band is familiar with the concept: when highly twisted, the band wraps around itself creating a supercoiled structure. In DNA, this structure - in its most compact form - is known as a plectoneme.
So far, scientists have only been able to study relatively small supercoiled DNA molecules, with typical sizes below 10 kilo-base pairs (kb). Handling larger molecules represents a considerable feat, mostly due to the fragile nature of the formation: “When extracting large plasmids, even a single base pair nick is enough to lose supercoiling” points out Aleksandre Japaridze from the EPFL and main author of the study published in Nano Letters. In the present study, however, researchers managed to look at much larger molecules: “When we started to look at the DNA at a bigger scale, strange things happened” says Fabrizio, who was in charge of the computational aspects of the study. At scales of 10 to 40 kb, the DNA molecule started to form an even denser self-organization structure than regular plectonemes, which is why they were dubbed: hyperplectonemes.
The researchers also went on to study the structural, nanomechanic and dynamic properties of these structures, thereby providing a mechanistic insight into the critical role of DNA topology in genetic regulation.
Reference: Hyperplectonemes: A Higher Order Compact and Dynamic DNA Self-Organization
Aleksandre Japaridze, Georgi Muskhelishvili, Fabrizio Benedetti, Agni F. M. Gavriilidou, Renato Zenobi, Paolo De Los Rios, Giovanni Longo, and Giovanni Dietler
Nano Letters Article ASAP
AFM image of a 42 kb DNA molecule forming hyperplectonemes.
Image courtesy of the Laboratory of Physics of Living Matter (EPFL)