First ever observation of the unwinding of a double-stranded DNA helix

The disintegration of DNA occurs within a number of natural processes essential to life: mutagenesis (change in the DNA sequence), synthesis, recombination and repair

[Translation by Dr. Nachmani Moshe]
Scientists have developed a method for producing biological crystals that allow researchers to observe - for the first time ever - the unraveling of DNA double helices. The researchers also developed a computer simulation that allows us to see this process with our own eyes.

Scientists from Spain's National Center for Cancer Research (CNIO) have developed a method for producing biological crystals that allow researchers to observe - for the first time ever - the unraveling of DNA double helices. The researchers also developed a computer simulation that allows this process to be visualized. The research findings have long been published in the scientific journal Nature Structural & Molecular Biology.

"We knew that enzymes, or proteins, are responsible for the disassembly of these double helices, but we did not know exactly how this mechanism works," said the lead researcher. "In our study, we describe in great detail the dynamics of this basic biological reaction mediated by a defined enzyme (I-Dmol). Our observations can be extrapolated to many other families of enzymes with the same or similar function."

The disintegration of DNA occurs within a number of natural processes essential to life: mutagenesis (change in the DNA sequence), synthesis, recombination and repair. In the field of molecular biology, DNA can also be prepared synthetically. Once the exact mechanism responsible for this breakdown is revealed, it will be possible to use this knowledge in a number of biotechnological applications, starting with the correction of mutations in order to treat genetic diseases and ending with the development of genetically modified organisms.

Enzymes function as dynamic systems with a high level of specialization. Their discharge function, explains the lead researcher, can be compared to a fabric cutting machine that has been specially designed so that it "cuts only when a specific combination of colors passes under its blade." In this case, the researchers focused on observing the spatial changes that occurred in the active site of the enzyme I-Dmol - that part of the enzyme that includes the amino acids that function as the blade that cuts the DNA double helix. By changing the temperature balance and the acidity level (pH), the researchers were able to delay a chemical reaction that normally lasts microseconds so that it lasts for up to ten days. Under these conditions, the researchers were able to create a slow-motion video of the entire process.

"By introducing a cation of the metal magnesium, we were able to initiate the enzyme reaction and then produce biological crystals and freeze them to a temperature of minus 200 degrees Celsius," said the researcher. "In this way, we were able to collect 185 crystal structures that represent all the spatial changes that occurred in each of the reaction steps." In the last step and with the help of computer analysis, the researchers were able to illustrate the seven intermediate stages of the splitting process of a DNA double helix. "Our findings are very fascinating because understanding this mechanism will provide us with the information we need to design and design similar enzymes that will function as precise molecular scissors, enzymes that are essential tools for genome modification," concludes and says the lead researcher.

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