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DNA replication is vital for all life forms, but in some organisms it can be prevented by DNA sequence changes, called "supercoils". If too many superwinds are allowed to form, cells vital to life will die.
A molecular machine, called DNA gyrase, which is found in bacterial cells but not in human cells, relaxes twists to allow DNA replication to continue normally, but up to now, one can did not understand how to do it in real time in real living cells. .
The process is of particular interest to drug developers because if the DNA gyrase can be successfully interrupted to prevent the cells of the bacterial DNA from twisting, the bacteria will die and the threat of an infection from the prevented host.
The York University team, in collaboration with the John Innes Center of Oxford and the Adam Mickiewicz University of Poland, used a special laser microscope to illuminate a fluorescent protein that makes the gyrase DNA yellow. This allowed scientists to see inside a bacterial cell and, for the first time, observe how molecular mechanisms prevent DNA twists.
Professor Mark Leake, of the Department of Biology and Physics at the University of York, said: "By using modified fluorescent proteins, the DNA gyrase can become yellow while the cellular machinery used to replicate the DNA can be marked different glowing proteins.
"These separate colors can then be split into different detection channels to help pinpoint DNA gyrase precisely relative to the exact point where DNA replication occurs in a single living bacterial cell."
The researchers found that DNA gyrase concentrates its relaxation activities by twisting just before the moment the DNA is replicated in a cell.
Professor Leake said: "Molecular machines that perform DNA replication along DNA, but these works can result in tiny DNA twists at the nanoscale that you'll accumulate in front of the replication machines, just like tangled cables on the back of your TV.
"We have now shown that several dozen gyrase DNA molecules actively bind to an area directly in front of the replication machinery and soften the DNA nano-twists faster than the replication machinery itself." does not move along the DNA.
"They basically prevent the creation of a" twist barrier "that would prevent the replication machinery from moving along DNA, replicating and killing the cell."
DNA gyrase is a target for a number of different antibiotics, but with the emergence of several 'super-insects' resistant to antibiotics, it is more urgent to understand the functioning of bacterial cells in real time.
Professor Leake said, "Now that we know how DNA gyrase really plays its role in living bacteria, we can help design new types of drugs that can prevent DNA gyrase to work, which will allow the drugs to be more targeted and ultimately kill dangerous bacterial infections in humans.
"Human cells have similar mechanisms for solving DNA twists but use different molecular machines, and our work on DNA gyrase in bacteria provides us with valuable information about the generalized mechanisms governing the functioning of the DNA." this clbad of remarkable biomolecules for all organisms. "
The research is published in the journal Nucleic acid research.
This article has been republished from documents provided by the University of York. Note: Content may have changed for length and content. For more information, please contact the cited source.
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