Scientists have discovered how and when DNA replicates inside cells.

Researchers first identified DNA replication in the 1950s, but have since struggled to understand the underlying mechanisms.

"It's been quite a mystery," David Gilbert, professor of molecular biology at Florida State University, said in a news release. "Replication seemed resilient to everything we tried to do to perturb it. We've described it in detail, shown it changes in different cell types and that it is disrupted in disease. But until now, we couldn't find that final piece, the control elements or the DNA sequences that control it."

In an attempt to disrupt the replication's timing, Gilbert and doctoral student Jiao Sima engineered dozens of genetic mutations on DNA molecules. The experiments failed to provide insight.

In what the researchers described as a "Hail Mary" approach, Gilbert and Sima studied a single DNA segment in the highest 3D resolution possible. Their analysis revealed three sequences regularly in contact with each other around a DNA molecule.

Using CRISPR, scientists deleted the three sequences simultaneously. To their surprise and relief, the deletion interrupted DNA replication and altered the DNA molecule's structure.

"Removing these elements shifted the segment's replication time from the very beginning to the very end of the process," Gilbert said. "This was one of those moments where just one result knocks your socks off."

Researchers described their breakthrough in the journal Cell.

"We have for the first time pinpointed specific DNA sequences in the genome that regulate chromatin structure and replication timing," Sima said. "These results reflect one possible model of how DNA folds inside cells and how these folding patterns could impact the hereditary materials' function."

Researchers think the disruption of DNA replication could explain the development of certain diseases.

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