The shape and structure of supercoiled DNA is far more complex and dynamic than the widely accepted, traditional “double helix” terminology long accepted by molecular biologists indicates, according to new research published Monday in the journal Nature Communications.
The double helix model was first described by Francis Crick and James D. Watson in the 1950s, after the duo used X-ray diffraction and mathematical formulas to describe the structure and the shape of nucleic acids. Now, however, researchers from the Baylor College of Medicine and the University of Leeds have used cutting-edge technology to make a surprising discovery.
Using powerful microscopy techniques and supercomputer simulations, they found that DNA does not actually have a rigid and static double helix form. Rather, they observed that the acids are fluid and dynamic, morphing into a variety of different shapes, including figure-eights.
“When Watson and Crick described the DNA double helix, they were looking at a tiny part of a real genome, only about one turn of the double helix,” Dr. Sarah Harris of the School of Physics and Astronomy at the University of Leeds explained in a statement. “This is about 12 DNA ‘base pairs’, which are the building blocks of DNA that form the rungs of the helical ladder.”
“Our study looks at DNA on a somewhat grander scale – several hundreds of base pairs – and even this relatively modest increase in size reveals a whole new richness in the behavior of the DNA molecule,” she added. To put that into perspective, there are about three billion base pairs that comprise the complete set of instructions in human DNA.
Discovery could lead to the development of new medicines
Since there is so much molecular information, it needs to be organized and coiled up tightly in order to fit into a cell nucleus, and in order to fully understand the structure of DNA in this state, the researchers needed to replicate this process. Since they could not coil linear DNA, Dr. Harris and her colleagues had to make circles and use the ends to trap the winding.
They wound and unwound the small-scale DNA circles one turn at a time to investigate how this process changed what the circles looked like, and came up with a test to ensure that these minute strands of genetic information behaves the same way as full-length DNA strands in the cells.
To do so, they took an enzyme that manipulates the twisting of DNA and found that it relieved the winding stress from even the most supercoiled of the circles, indicating that the behavior of the DNA in these circles was the same as that encountered by the enzyme in the body. They then used cryo-electron tomography, a technique which involves freezing biologically active material, and finally used a powerful microscope to take three-dimensional images of the results.
They found that coiling the DNA circles caused them to form a variety of unexpected shapes, including sharp bends, figure-eights, handcuffs, or even rods. These images were then compared to those generated in supercomputer simulations, which showed how DNA constantly alters its shape in order to form a vast array of different structures, not just a static double-helix.
Knowing the shape of DNA when it’s in a cell could lead to the development of better antibiotics or cancer-treating medications, “because the action of drug molecules relies on them recognizing a specific molecular shape – much like a key fits a particular lock,” Dr. Harris explained.
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Feature Image: Thana Sutthibutpong
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