Why abnormal four-strand DNA molecules lead to cancer

(ORDO NEWS) — Two thin threads twisted together in a spiral – this is the well-known form of the DNA molecule. But sometimes DNA can form a rare quadruple helix, and this strange structure is strangely associated with cancer.

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

In a new study published in the journal Nature Communications, the team described how certain proteins cause the breakdown of the G-quadruplex; in the future, their work could lead to the creation of new drugs that hijack four-stranded DNA and disrupt its activity. For example, drugs can interfere when odd DNA promotes cancer growth.

“There is growing evidence that G-quadruplexes play an important role in a wide variety of processes vital to both healthy body and a variety of diseases,” study author Ben Lewis of the Department of Chemistry at Imperial College London writes.

According to the statement, in general, G-quadruplexes occur in cancer cells much more often than in healthy cells.

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 the display of this structure directly in living cells,” explains Lewis. In other words, scientists needed a more reliable way to observe these DNA molecules in action.

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 just measuring the brightness of the light, which changes with the concentration of the DNA molecules, the team also tracked how long the molecules glowed for.

Tracking how long the light persists helped the team see how various other 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 strands of four-stranded DNA and trigger their breakdown.

They also identified other molecules that bind to DNA. Future studies of such molecular interactions could help scientists develop drugs that affect many cellular processes and can save a person even from serious pathologies.


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