Rare four-stranded DNA first seen in action

(ORDO NEWS) — Two thin strands twisted together in a spiral: this is the iconic shape of the DNA molecule. But sometimes DNA can form a rare quadruple helix, and this strange structure can play an important role.

Little is known about the four-stranded DNA known as G-quadruplexes, but scientists have now developed a new way to detect these strange molecules and observe their behavior in living cells.

In a new study published Jan. 8 in the journal Nature Communications , the team described how certain proteins cause the G-quadruplex to break down; in the future, their work may lead to the creation of new drugs that hijack four-stranded DNA and disrupt its activity.

“There is growing evidence that G-quadruplexes play an important role in a wide range of vital processes and in a variety of diseases,” said study author Ben Lewis of the Faculty of Chemistry at Imperial College London in a statement.

Overall, G-quadruplexes occur more frequently in cancer cells than in healthy cells, according to the statement.

Various studies have linked the presence of four-stranded DNA to the rapid division of cancer cells, a process that leads to tumor growth; Therefore, scientists theorized that targeting strange DNA with drugs could slow or stop this rampant cell division. Several studies are already supporting this idea.

“But the missing link was displaying this structure directly in living cells,” Lewis said. In other words, the scientists needed a better way to observe these DNA molecules in action.

New research begins to fill in the missing knowledge.

G-quadruplexes can form either when a single double-stranded DNA molecule folds on its own, or when multiple DNA strands are joined together in a single nucleic acid known as guanine, one of the building blocks of DNA.

To find this bizarre DNA in cells, the team used a chemical called DAOTA-M2, which emits fluorescent light when it binds to G-quadruplexes. Rather than measuring only the brightness of the light, which changes based on the concentration of DNA molecules, the team also tracked how long it glowed for.

Tracking how long the light stays on helped the team see how different molecules interact with four-stranded DNA in living cells.

When the molecule clings to a strand of DNA, it displaces the glowing DAOTA-M2, causing the light to dim faster than if the chemical was left in place. Using these techniques, the team identified two proteins called helicases that unwind the four-stranded DNA strands and trigger their breakdown.

They also identified other molecules that bind to DNA; future research into these molecular interactions could help scientists develop drugs that bind to DNA.


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