Untwisting DNA Reveals New Force that Shapes Genomes

 

    Advanced microscope technology has allowed for the tertiary structure of DNA strands to better be understood and allowed for scientists to visualize how the genome organizes into these 3D structures. This new machinery uses high power lasers alongside chemical conditions that track fluorescent molecules to provide 10 times higher resolution than conventional microscopy. Prior to this new microscope technology it was not possible to analyze the tertiary structures of DNA closely. The new microscopes helped scientists draw correlations between the specific way DNA is transcribed and how it supercoils to form tertiary structures. Transcription was found to generate a force that moves across DNA strands like ripples through water. This is due to structural proteins known as cohesions that "surf" across DNA strands changing the shape of the genome in the process. Researchers believe that the discovery of the way cohesions affect the structure of DNA can help understand more about genetic and developmental disorders as it may be possible to draw correlations between diseases and tertiary structure folds. As DNA is condensed within a cell it forms many loops and coils which cause different sections of the DNA to interact with one another, allowing for individual cells to switch different information on and off. This new advancement shows that transcription aids in the process of determining which parts of the DNA fold to interact with each other. Until recently scientists were only able to predict where tertiary DNA loops were located but not their shape or what caused the coiling to form. The possibilities for this advanced form of microscopy are still being discovered.

Article Link: https://www.sciencedaily.com/releases/2021/07/210722113007.htm

Related Link:   https://www.ncbi.nlm.nih.gov/books/NBK26880/

 

Supercoil DNA

“By regulating access to the genetic code, DNA supercoiling strongly affects DNA metabolism. Despite its importance, however, much about supercoiled DNA (positively supercoiled DNA, in particular) remains unknown. Here we use electron cryo-tomography together with biochemical analyses to investigate structures of individual purified DNA minicircle topoisomers with defined degrees of supercoiling. Our results reveal that each topoisomer, negative or positive, adopts a unique and surprisingly wide distribution of three-dimensional conformations. Moreover, we uncover striking differences in how the topoisomers handle torsional stress. As negative supercoiling increases, bases are increasingly exposed. Beyond a sharp supercoiling threshold, we also detect exposed bases in positively supercoiled DNA. Molecular dynamics simulations independently confirm the conformational heterogeneity and provide atomistic insight into the flexibility of supercoiled DNA. Our integrated approach reveals the three-dimensional structures of DNA that are essential for its function. ” -abstract from Nature

Using a combination of approaches supercoiling causes DNA to adopt large conformational variability. Unpaired bases and localized distortions contribute to this variability both by relieving torsional strain and by providing flexible hinges. Positive and negative supercoiling are accommodated differently.