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DNA consists of two strands, composed of sugar molecules and phosphate groups. Between these two strands, there are nitrogenous bases, the compounds that constitute the genes, with hydrogen bonds between them. Until now, it was thought that it was these hydrogen bonds that made it possible to bind the two strands. But a new study, published in the Proceedings of the National Academy of Sciences, shows that the secret of the helical structure of DNA lies in the fact that the molecules have a hydrophobic interior, in an environment consisting mainly of water.
For DNA to be read, replicated or repaired, the DNA molecules must open themselves. This occurs when cells use a catalytic protein to create a hydrophobic environment around the molecule. Image Credit: Yen Strandqvist / Chalmers University of Technology.
Reproduction involves DNA base pairs that dissolve and open. The enzymes then copy both sides of the helix to create a new DNA.
When it is a question of repairing the damaged DNA, the damaged areas are subjected to a hydrophobic environment, to be replaced.
A catalytic protein creates the hydrophobic environment. This type of protein is at the heart of all DNA repair, which means it could be the key to fighting many serious diseases.
Understanding these proteins could provide a lot of new information on how we could, for example, fight resistant bacteria or even potentially cure cancer.
"Bacteria use a protein called RecA to repair their DNA, and our findings could provide new insights into how this process works, potentially offering methods to stop them and kill the bacteria," said Dr. Bobo Feng, researcher. in the Department of Chemistry and Chemical Engineering at Chalmers University of Technology and his colleagues.
"In human cells, a protein called Rad51 repairs DNA and fixes mutated DNA sequences, which could otherwise lead to cancer."
"To understand cancer, we need to understand how DNA is repaired. To understand this, we must first understand the DNA itself, "said Dr. Feng.
"Until now, we have not done it because we thought hydrogen bonds were what held him. Now, we have shown that instead, it is the hydrophobic forces that are behind. "
"We have also shown that DNA behaves totally differently in a hydrophobic environment. This could help us understand the DNA and its repair. "
"Nobody had previously placed DNA in a hydrophobic environment like this one and studied its behavior, so it 's no wonder no one has discovered it until the end of the day. now."
The authors studied the behavior of DNA in a more hydrophobic environment than normal, method with which they were the first to experiment.
They used the hydrophobic solution of polyethylene glycol and, step by step, modified the environment of the DNA, which went from the naturally hydrophilic environment to a hydrophobic environment.
They wanted to know if there is a limit to which DNA begins to lose its structure, while DNA has no reason to bind because the environment is no longer hydrophilic.
Scientists have observed that as the solution reaches the boundary between hydrophilic and hydrophobic, the spiral shape characteristic of the DNA molecules begins to unravel.
After a closer inspection, they found that when the base pairs separated from each other (due to external influence or simply because of random movements), holes formed in the structure, which allowed the water to infiltrate.
Because DNA wants to keep its interior dry, it presses, the base pairs pulling together to get the water out. In a hydrophobic environment, this water is missing, so the holes remain in place.
"The cells want to protect their DNA and not expose it to hydrophobic environments, which can sometimes contain harmful molecules," said Dr. Feng.
"But at the same time, the cells' DNA must open up to be able to be used. We think that the cell retains its DNA in an aqueous solution most of the time, but as soon as a cell wants to use something with its DNA, like reading it, copying it or repairing it, it exposes the DNA to a hydrophobic environment. "
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Bobo Feng et al. 2019. Hydrophobic catalysis and the potential biological role of DNA de-stacking induced by effects on the environment. PNAS 116 (35): 17169-17174; doi: 10.1073 / pnas.1909122116
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