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DNS with blur: discovery could improve antibiotic development

DNS replication is essential for all types of lives, but in some organisms it can be prevented by cutting the DNA sequence called "supercoil". If too many supercelles are allowed to form, the life-damping cells will die.

A molecular machine called DNA gyrase found in bacterial cells, but not in human cells, relaxes the clippings, allowing DNA replication to continue as usual, but until now there was a limited understanding of how it occurs in real live cells in real time.

This process is particularly important for drug developers, because if the DNA gyrase can be successfully stopped because it works to stop the changes that occur in bacterial DNA cells, the bacteria will die and the risk of infection to the host will be eliminated.

The York University team, in collaboration with John Inne Center, Oxford and Adam Mickiewicz University, in Poland, used a special laser microscope to shine a light on a fluorescent protein that produces a yellowish-yellow DNA spray. This allowed scientists to see the bacterial cell and for the first time observe how the molecular machine prevents DNA deformation.

Professor Mark Leake of York's Department of Biology and Physics said: "Using modified fluorescent proteins, DNA gases can make the yellow gloss, while a cellular machine used to actually replicate DNA can be labeled with a variety of reddish-shining proteins.

"Then, these individual colors can be split into different channels of the detector to accurately determine the state of the DNA gase relative to the exact point at which DNA replication really takes place in one living bacterial cell."

Researchers have discovered that the DNA gyrus draws attention to its twist-relaxation activity at the exact point in which DNA is replicated in the cell.

Professor Lick said: "Molecular machines that perform DNA replication state by DNA, but this work can lead to a small DNA nano-cuts that accumulate in front of replication devices, just like the compressed cables on the back of the TV.

"Now we have shown that several dozen DNA gyrase molecules actively bind to the area directly in front of the replication device and relax DNA nano-cut faster than the replication machine itself is moving through the DNA.

"It essentially eliminates the" demolition barrier "that will destroy, which will stop the replication equipment from interrupting replication and killing the cell."

DNA gyrase is the goal of a variety of antibiotics, but with several "super-bugs" that cause antibiotic resistance, it's urgent to understand how bacterial cells work in real time.

Professor Lick said: "Now that we know how the DNA gyrase really plays its role in living bacteria, we can help develop new types of drugs that can stop DNA girazes acting, which will make drugs more targeted and ultimately kill dangerous bacterial infections in humans.

"Human cells have similar mechanisms to resolve DNA deformities, but use different molecular machines, and our work with DNA gyrase in bacteria gives us a valuable insight into the general mechanisms that regulate the effect of this class of outstanding biomolecules on all organisms."

The study is published in the journal Nucleic Acid Research.

This article has been republished from the materials provided by York University. Note The material may have been edited due to its length and content. For more information, please contact the source quoted.

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