Supercoiled DNA has more dynamic shape than double helix
Credit: Bio Quick News ” 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”, said Harris as reported by EurekAlert. The complete human genome contains three billion base bares, all of which are wound up tight and squeezed into a cell’s nucleus.
What the researchers saw turned the traditional notion of DNA’s stable double helix structure upside down and inside out.
“This is because the action of drug molecules relies on them recognizing a specific molecular shape – much like a key fits a particular lock”, Harris said in a statement. They’ve discovered that, not only are long DNA strands enormously complex, they constantly wiggle and morph into different shapes. The construction, formed by double-stranded molecules of nucleic acids, was first uncovered by researchers James Watson and Francis Crick, and popularized in Watson’s 1978 guide “The Double Helix: A Private Account of the Discovery of the Construction of DNA”. “Each of these different structures facilitates how DNA interacts with proteins, other DNA and RNA, and anticancer drugs, adapting to the cell processes required”.
The standard helix we often see is perhaps no more than a dozen DNA base pairs in sequence.
The researchers believe that the understanding of how DNA behaves inside a cell will help develop targeted therapies and, better medicines and antibiotics for cancer treatment.
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.
Examining the tiny, twisted DNA circles that were created, the researchers used the enzyme human topoisomerase II alpha to determine if the circles behaved in the same way as full-length DNA strands within human cells. The take a look at confirmed that the enzyme relieved the winding stress from all the supercoiled circles, even probably the most coiled ones, which is its regular job within the human physique. After that, they used special microscopy to visualize their new shapes, while also developing models of them on the computer. This result means that the DNA in the circles must look and act like the much longer DNA that the enzyme encounters in human cells.
“Among the circles had sharp bends, a few had been determine-8s, and others seemed like handcuffs or racquets and even stitching needles. A few looked like rods because they were so coiled”, said Irobalieva. This microscopy technique makes it easier for researchers to observe tiny and frequently changing biological samples.
Dr Harris concludes: “We are sure that supercomputers will play an increasingly important role in drug design”. “We are trying to do a puzzle with millions of pieces, and they all keep changing shape”, she says.