A research team from Florida State University has opened up a decades-old mystery about how critical cellular processes are regulated and what that means for future genetic studies.
In cells, DNA and related materials replicate periodically, a process that is important for all living organisms. This contributes to everything, from how the body responds to disease to hair color. DNA replication was identified in the late 1950s, but since then researchers around the world have tried to understand exactly how this process is organized. Now they know.
David Gilbert, professor of Molecular Biology J. Herbert Taylor, and doctoral student Jiao Sima published a paper today in the journal Cell which shows there are specific points along the DNA molecule that control replication.
"It's quite a mystery," Gilbert said. "Replication seems resilient to everything we try to disturb it. We have explained it in detail, showing it changes in various cell types and it is disrupted by disease. But until now, we cannot find the last part, the control element or the DNA sequence that controls it. "
In particular, the post of professor Gilbert was to honor former Florida State professor named J. Herbert Taylor. Taylor showed how diverse chromosome segments duplicated in the late 1950s and published more than 100 papers on the structure and replication of chromosomes. About 60 years later, Gilbert determined how replication was regulated.
Sima has worked with Gilbert in the laboratory and is approaching a hundred genetic mutations in DNA molecules, hoping to see some kind of results that will further explain how the replication process works. At the point of frustration, Gilbert said they came up with "Mary's greeting".
Gilbert and Sima examined one segment of DNA in 3-D resolution as high as possible and saw three sequences along the DNA molecules that often touched each other. The researchers then used CRISPR, a sophisticated gene editing technology, to eliminate these three areas simultaneously.
And with that, they found that these three elements together are the key to DNA replication.
"Removing these elements shifts the replication time of the segment from the beginning to the end of the process," Gilbert said. "This is one moment where only one result knocks your socks."
In addition to the effects of replication, the removal of three elements causes the 3-D structure of DNA molecules to change dramatically.
"We first showed a specific DNA sequence in the genome that regulates chromatin structure and replication time," Sima said. "These results reflect a possible model of how DNA folds in cells and how this fold pattern can affect the function of hereditary material."
A greater understanding of how regulated DNA replication can open up new pathways of research in genetics. When the replication time is changed – as in the Gilbert and Sima experiments – it can completely change how the genetic information of a cell is interpreted.
This can be important information when scientists deal with complex diseases where replication time is disrupted.
"If you multiply at different times and places, you might arrange a completely different structure," Gilbert said. "A cell has different things available to it at different times. Changes when something replicated changes the packaging of genetic information."
A new understanding of genetic replication can help in fighting cancer