More dynamic strucuture of supercoiled DNA revealed in 3D-imaging
The double helix shape of DNA is the popular way to imagine DNA. It also loops into a menagerie of fantastical shapes, new research finds.
Researchers examined three-dimensional pictures of supercoiled DNA and found that it could change its shape in a number of ways that go beyond the double helix model by Watson and Crick.
To understand the structure of DNA when it is crammed into cells, the researchers needed to replicate this coiling of DNA.
DNA’s double helix shape, discovered by researchers Francis Crick and James Watson, is one of science’s most famous images. In their study, they wound or unwound a single turn at a time the DNA double helix comprising their circles and asked how the winding changed what the circles looked like, using very powerful microscopes. “This is about 12 DNA “base pairs, ‘ which are the building blocks of DNA that form the rungs of the helical ladder”.
“The next step is to start adding the other components of the cell or anticancer drugs to see how the DNA shapes change”, said co-author Dr Jonathan Fogg, of the BMC. “Even that much of an increase in size reveals a whole new richness in the behavior of the DNA molecule”, Harris said.
“Some of the shadows had strong ducks, a few have been figure-8s, as well as others gave the impression of shackles or racquets or perhaps even stitching sharp needles. A few looked like rods because they were so coiled”, the study’s lead author, Rossitza Irobalieva, a biochemist at the Baylor College of Medicine in Houston, said in a statement.
The researchers devised a test to make sure that the tiny twisted up DNA circles that they made in the lab were biologically active.
They used an enzyme named “human topoisomerase II alpha” that influences the twist of DNA.
In a study published this week in the journal Nature Communications, Dr. Sarah Harris from the University of Leeds suggests that studying these supercoiled DNA shapes could enable us to develop better drugs and treatments, especially treatments that directly affect the DNA, like chemotherapy for example. First, scientists at Baylor made little circles of DNA and then used a microscopy technique known as cryo-electron tomography to create detailed images of them. Findings reveal that DNA is flexible and versatile.
Typically, the DNA helix is formed when complementary base pairs – such as the nucleotide adenine and its partner guanine – bind together, forming a bridge across the helix. The new perspective revealed a varied and complex design.
These tiny circles were about 10 million times shorter than an actual DNA strand, but by the standards of modern genetics, these structures themselves are quite massive and hard to work with. She is confident about the increasing role of supercomputers in the development of drugs.