Calling Through the DNA Cord: A Recently Discovered Genetic “Switch Over.”

According to the Weizmann Institute of Scientific scientists, proteins can connect through DNA, performing a long-distance dialogue that functions as a type of genetic “switch.” They discovered that the binding of proteins to one point of a DNA molecule could affect an additional binding point at a further point. This “peer impact” triggers particular genes. This effect had previously been seen in artificial systems, yet the Weizmann study is the first to show it happens in the DNA of living organisms.

A team leaded by Dr. Hagen Hofmann of the Chemical and Structural Biology Department made this finding while researching a strange event in the soil bacteria Bacillus subtilis. A tiny minority of these bacteria show a one-of-a-kind ability to enhance their genomes by using up bacterial gene sectors spread in the surrounding soil. This ability relies on a protein called ComK, a transcription factor that binds to the DNA to activate the genes that make scavenging feasible. However, it was unidentified how exactly this activation works.

According to the Weizmann Institute of Scientific scientists, proteins can connect through DNA, performing a long-distance dialogue that functions as a type of genetic “switch.” They discovered that the binding of proteins to one point of a DNA molecule could affect an additional binding point at a further point. This “peer impact” triggers particular genes. This effect had previously been seen in artificial systems, yet the Weizmann study is the first to show it happens in the DNA of living.Team Scientist Dr. Gabriel Rosenblum led this research study, in which the researchers investigated the microbial DNA using innovative biophysical tools– single-molecule FRET and cryogenic electron microscopy. Mainly, they concentrated on both sites on the DNA molecule to which ComK proteins bind.

They discovered that when 2 ComK molecules bind to one of the sites, it triggers a signal that facilitates the binding of 2 extra ComK particles at the 2nd site. The call can travel between the sites because physical modifications caused by the original healthy proteins’ binding create tension that is transferred along with the DNA, like bending a rope from one end. When all four particles are bound to the DNA, a threshold is passed, switching on the bacterium’s gene scavenging capability.

“We were shocked to find that DNA, in addition to holding the genetic code, acts as a communication cable, transferring information over a reasonably long distance from one healthy protein binding point to another,” Rosenblum claims.

By manipulating the bacterial DNA and keeping an eye on the effects of these manipulations, the researchers cleared up the details of the long-distance interaction within the DNA. They discovered that for communication– or cooperation– between 2 points to occur, these points must be situated at a specific distance from each other, and they face the same direction on the DNA helix. Any deviation from these two conditions– for example, augmenting the distance– damaged the communication. The sequence of hereditary letters running between the two sites was found to have little effect on this communication. In contrast, a break in the DNA interrupted it entirely, further evidencing that this communication happens through a physical link.

Knowing these details may assist in developing molecular switches of desired strengths for various of applications. The latter may involve genetically designed microorganisms to tidy up environmental pollution or synthesizing enzymes as medicines.

“Long-distance communication within a DNA molecule is a brand-new kind of regulatory device– one that opens previously unavailable techniques for creating the genetic circuits of the future,” Hofmann states.

Originally published on Scitechdaily.com. Read the original article.

Reference: “Allostery through DNA drives phenotype switching” by Gabriel Rosenblum, Nadav Elad, Haim Rozenberg, Felix Wiggers, Jakub Jungwirth and Hagen Hofmann, 20 May 2021, Nature Communications.
DOI: 10.1038/s41467-021-23148-2

The research team included Dr. Nadav Elad of Weizmann’s Chemical Research Support Department; Dr. Haim Rozenberg and Dr. Felix Wiggers of the Chemical and Structural Biology Department; and Jakub Jungwirth of the Chemical and Biological Physics Department.

Dr. Hagen Hofmann is the incumbent of the Corinne S. Koshland Career Development Chair in Perpetuity.