Quadruple-helix DNA
The DNA of human cells is generally in a double-helix form, and quadruple-helix is rare. Scientists have recently discovered a chemical probe that can directly observe the interaction of quadruple-helix DNA with other molecules in human cells, uncovering the role of quadruple-helix DNA within various natural cellular processes.
Scientists have found more quadruple-helix DNA in cancer cells and therefore believe that quadruple-helix DNA plays an important role in cancer. A recent study, published in the journal Nature Communications, used chemical probes to see how quadruple-helix DNA is unspooled by the action of specific proteins, which could help find molecules that specifically bind quadruple-helix DNA and thus develop drugs that target to combat their activity.
“Different DNA morphologies have a huge impact on all the processes involved in, for example, reading, replication and gene expression,” says Ben Lewis of Imperial College London’s chemistry department, one of the researchers.
“There is growing evidence that quadruple helix DNA has important implications for multiple important processes of Life as well as a wide range of diseases, but the missing link is the direct observation of the activity of this structure within living cells.”
Quadruple helix DNA is so rare, Lewis said, that ordinary detection methods to find molecules with this genetic structure are “harder than finding a needle in a haystack.
The group found the DAOTA-M2 chemical probe, which glows when it encounters a quadruple-helix DNA structure. It was found that the duration of the glow, rather than the brightness, should be monitored to get a better view of these rare molecules.
The team used this probe to directly observe the interaction of quadruple-helix DNA with two decapping proteins in living cells. They saw that more quadruple-helix DNA was observed if these unscrewing enzyme proteins were removed, implying that these proteins act to unscrew the quadruple-helix DNA.
Researcher Jean-Baptiste Vannier said, “Previously, we could only understand the role played by these unspinase proteins indirectly, now we can see them directly inside living cells.”
The researchers also looked at other molecules interacting with the four-helix DNA inside living cells. When a molecule enters a cell with this DNA structure, the molecule will take the place of DAOTA-M2, thus shortening the Time it takes for it to glow.
This allows researchers to study the activity of more molecules, such as those that do not glow and are not visible under the microscope, within the cell nucleus.
Ramon Vilar, professor of chemistry at Imperial College London, said, “Many researchers are interested in molecules bound to quadruple helix DNA, examining their potential as anti-cancer drugs. Our new approach could help develop these potential new drugs.”
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