Researchers from Cambridge University have discovered four-stranded “quadruple helix” in living human cells. Quadruple helix DNA structures take shape in regions of DNA that are full of the building block guanine. The findings represent more than a decade of research by scientists to reveal these structures in human cells. The research also reveals clear connections between concentrations of quadruple helix DNA and the process of DNA replication, which is an important part of cell division and production.
Researchers believe that their findings could lead to better cancer treatments. For example, by targeting quadruple helix DNA with synthetic molecules that ensnare and contain these DNA structures, researchers think that it may be possible to stop the out-of-control cell generation at the root of cancer.
Professor Shankar Balasubramanian from the University of Cambridge’s Department of Chemistry and Cambridge Research Institute says that researchers are seeing links between trapping the quadruple helix DNA structures with molecules and the ability to block cell division. Balasubramanian and his team found that these structures are more likely to be found in genes of cells that are quickly dividing, like cancer cells.
While previous research revealed that quadruple helix DNA could form in the test tube, this study was the first to prove that they can form in the DNA of human cells.
Dr. Julie Sharp, senior science information manager at Cancer Research UK, says that the next step is to determine how to target these structures in tumor cells. For scientists, this study proves that the story of DNA continues to “twist and turn.”
Study leader Giulia Biffi, a researcher in Balasubramaninan’s lab at the Cambridge Research Institute, was able to create antibody proteins that identify and attach to areas of human DNA rich in the quadruplex structures, affirming their existence in living human cells.
Using fluorescence to mark the antibodies, the researchers could then recognize “hot spots” for the appearance of quadruple helix DNA.
Researchers found that a marked increase in quadruplex DNA was seen during the “s-phase” when the cell replicates DNA before it divides.
They believe that potentially harmful cellular activity can be targeted with synthetic molecules or other types of treatments.
Trapping the quadruplex DNA with synthetic molecules allowed researchers to “sequester” and “stabilize” them, according to Balasubramanian. This finding will offer researchers important information on how they might be able to stop cell division in the future.
The study also demonstrated that if an inhibitor is used to block DNA replication, quadruplex levels drop, suggesting that DNA is dynamic, with structures constantly being formed and unformed.
According to Balasubramanian, quadruple helix DNA may be key to new methods of selectively preventing the generation of cancer cells.
The study’s findings are described in detail in the journal Nature Chemistry.
Photo credit: Jean-Paul Rodriguez and Giulia Biffi.