Researchers at the Chalmers University of Technology in Sweden have refuted the prevailing theory of how DNA binds itself. It is not, as is generally believed, hydrogen bonds that connect the two sides of the DNA structure. Instead, water is the key. The discovery opens doors to new insights in research in medicine and life sciences. The results are published in PNAS .
DNA consists of two strands consisting of sugar molecules and phosphate groups. Between these two strands are nitrogen bases, the compounds that make up genes and between which there are hydrogen bonds. So far it has been generally assumed that these hydrogen bonds hold the two strands together.
Researchers at Chalmers University of Technology, however, show that the secret of the helical structure of DNA is that the molecules in an environment have a hydrophobic interior consisting mainly of water. The environment is therefore hydrophilic, while the nitrogenous bases of the DNA molecules are hydrophobic and push away the surrounding water. When hydrophobic moieties are in a hydrophilic environment, they group together to minimize exposure to water.
The role of hydrogen bonds, previously thought to be critical for the cohesion of DNA helixes, appears to have more to do with sorting the base pairs so that they link together in the correct order. The discovery is critical to understanding the relationship of DNA to its environment.
"Cells want to protect their DNA and not expose it to hydrophobic environments that can sometimes contain harmful molecules," says Bobo Feng, one of the researchers behind the study. "At the same time, the cells' DNA must open up to be used."
"We believe that the cell keeps its DNA in a water solution most of the time, but as soon as a cell desires to do something with its DNA, read, copy, or repair it, it sets the DNA to one hydrophobic environment. "
During reproduction, for example, the base pairs separate and open. Enzymes then copy both sides of the helix to generate new DNA. When repairing damaged DNA, the damaged areas are exposed to a hydrophobic environment to be replaced. A catalytic protein creates the hydrophobic environment. This type of protein is central to all DNA repair, which means it could be the key to fighting many serious diseases.
Understanding these proteins could provide many new insights, for example, to fight resistant bacteria or to potentially cure cancer. Bacteria use a protein called RecA to repair their DNA, and the researchers believe that their findings could provide new insights into how this process works ̵
In human cells, the protein repairs Rad51 DNA and fixes mutated DNA sequences that could otherwise cause cancer. "To understand cancer, we need to understand how DNA is repaired, and to understand that, we first have to understand the DNA itself," says Bobo Feng. "So far, we did not do that because we believed that hydrogen bonds hold it together, but now we've shown that the hydrophobic forces are behind it instead." We also showed that DNA behaves completely differently in a hydrophobic environment. No one has previously put DNA into a hydrophobic environment like this one and studied its behavior, so it's not surprising that no one has discovered it yet. "
The researchers also have investigates how DNA behaves in an environment that is more hydrophobic than normal – a method they were the first to experiment with. They used the hydrophobic solution of polyethylene glycol and gradually transformed the environment of the DNA from the natural hydrophilic to a hydrophobic environment. They wanted to find out if there is a limit to how DNA starts to lose its structure if DNA has no reason to bind because the environment is no longer hydrophilic. The researchers found that the characteristic spiral shape of the DNA molecules dissolves when the solution reaches the boundary between hydrophilic and hydrophobic.
On closer examination, they found that the base pairs split (due to external influences). or simply by accidental movements), holes are formed in the structure that allow the ingress of water. As the DNA tries to keep its interior dry, it contracts, bringing the base pairs back together to squeeze out the water. In a hydrophobic environment, this water is missing, leaving the holes in place.
"Hydrophobic catalysis and a possible biological role of DNA unstacking caused by environmental influences" has been published in Proceedings of the National Academy of Sciences ( PNAS ).
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Bobo Feng et al., Hydrophobic Catalysis and a Possible Biologic Role of Degradation Induced by Environmental Influences, Proceedings of the National Academy of Sciences (2019). DOI: 10.1073 / pnas.1909122116
DNA is held together by hydrophobic forces (2019, September 23)
retrieved on September 23, 2019
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