A team of researchers from the University of Florida uncovered a long-held secret about how the critical cellular process is regulated and what this may mean for the future study of genetics.
In cells, DNA and its associated material replicate at regular intervals, a process necessary for all living organisms. This contributes to everything from the body's response to disease to hair color. DNA replication was identified in the late 1950s, but since then, researchers around the world have not been able to understand exactly how this process is regulated. Now they know.
David Gilbert, Emeritus Professor of Molecular Biology J. Herbert Taylor and graduate student Jiao Sima published an article in the journal today cell which showed that there are certain points along the DNA molecule that control replication.
“It was quite a mystery,” said Gilbert. “Replication seemed to be resistant to everything we tried to do to break it. We described it in detail, showed that it changes in different types of cells and that it is broken in the course of the disease. But until now, we could not find this last part, the controls or DNA sequences that control it. "
It is noteworthy that Professor Gilbert is in honor of a former Florida State professor named J. Herbert Taylor. Taylor demonstrated how different segments of chromosomes are duplicated in the late 1950s, and published over 100 papers on chromosome structure and replication. After about 60 years, Gilbert determined how replication was regulated.
Sima worked with Gilbert in the laboratory and conducted about a hundred genetic mutations on DNA molecules, hoping to see some result that would better explain how the replication process worked. At the moment of disappointment, Gilbert said that they had attempted to “greet Mary”.
Gilbert and Sima examined one DNA segment in the highest possible three-dimensional resolution and saw three sequences along the DNA molecule, often in contact with each other. The researchers then used CRISPR, a sophisticated gene editing technology, to remove these three areas simultaneously.
And with this, they discovered that these three elements together were the key to DNA replication.
“Removing these items shifted the segment replication time from the very beginning to the very end of the process,” said Gilbert. "It was one of those moments when only one result knocks your socks off."
In addition to the effect on replication time, the removal of three elements led to a dramatic change in the three-dimensional structure of the DNA molecule.
“For the first time, we identified specific DNA sequences in the genome that regulate chromatin structure and replication time,” said Sima. "These results reflect one possible pattern of how DNA is folded inside cells and how these folding patterns can affect the function of hereditary materials."
A deeper understanding of how DNA replication is regulated opens up new ways for genetics research. When replication time changes, as it was in the Gilbert and Sima experiment, it can completely change the interpretation of the genetic information of the cell.
This can be important information, as scientists struggle with complex diseases when replication times are disrupted.
“If you duplicate in another place and time, you can put together a completely different structure,” said Gilbert. “A cell has different things available to it at different times. Change, when something copies, changes the packaging of genetic information. "
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