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Researchers at Brookhaven lab, Stony Brook and Rockefeller universities make new discoveries about double helix copying

Molecular biologist Huilin Li points to some of

Molecular biologist Huilin Li points to some of the work he and colleagues have done in DNA research. With him, from left, are Zuanning Yuan, a graduate student at Stony Brook University. and Jingchuan Sun of Brookhaven National Laboratory. Photo Credit: Brookhaven National Laboratory

Depictions of DNA's intricate replication choreography may soon change because of new insights into how the double helix copies itself and why this understanding provides lessons on mutations and cancer, scientists reported Monday.

Researchers at Brookhaven National Laboratory, Stony Brook and Rockefeller universities have found that DNA replication, which involves unwinding the double helix, does not occur as countless scientific illustrations have depicted it.

The research, reported in Nature Structural & Molecular Biology, suggests that while many of the basic units involved in the process have been aptly defined, their positions have not been accurately described until now.

Moreover, the research provides intriguing insight into how the molecular machinery of the double helix functions, including new possibilities about DNA "quality control" during cell differentiation.

Scientists now say everything from high school and college textbooks to YouTube videos and even detailed illustrations for scientific research will have to undergo a change.

"I have never been excited like this," said Huilin Li, a molecular biologist with joint appointments at Brookhaven and Stony Brook, who with his team, captured images of the "the replication fork," the splitting of each DNA helice. Using an electron microscope, Li glimpsed one of nature's deepest secrets: how proteins position themselves during replication of life's master molecule.

"It's not easy to find something that is totally unexpected. But in science some discoveries are more exciting than others, and this one is fundamental to biology," Li said.

In Manhattan, Michael O'Donnell, who heads Rockefeller's Laboratory of DNA Replication, said the finding will change how students understand DNA replication.

"It's a paradigm shift in thinking," said O'Donnell, the project's lead investigator. "We looked at [DNA replication] in budding yeasts, a model organism," he said referring to all higher organisms -- humans, honey bees, coffee trees, lice, mice and wombats, to name a few.

"Yeasts have all the same proteins involved in DNA replication as the human replication system. So this will change the pictures in textbooks."

O'Donnell said it is fitting that much of the new research occurred at Rockefeller, the institution where DNA was discovered in 1944.

He and Li focused on "the replisome," a bloc of proteins involved in unwinding the spiraling DNA ladder. Both helices must be duplicated in cell division. Much of this kind of research in the past had focused on bacteria. But scientists moved higher on the tree of life to get a sense of how the process occurs in humans.

They found to their surprise that higher organisms have more than 30 different gears -- proteins -- to make the replication machinery work.

Key among these gears is an enzyme called helicase, which unzips each helix into single strands.

But the team is changing scientific dogma because for years it was widely thought that two enzymes called polymerases trailed behind or below the helicase as it unzipped the strands. Polymerases are vital because they assemble each nucleotide, the building blocks of DNA.

The team uncloaked a surprise: one polymerase is positioned in front of the helicase, the other underneath.

"What's being described here is absolutely and completely a shift in what we know about DNA replication," said Benjamin Weeks, a professor of biology at Adelphi University.

Weeks, not part of the research, said he sees it changing how researchers approach the molecule in numerous areas of biological endeavor.

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