CUADRUPLEX

Quadruple Helix DNA Exists In Human Genome

60 years after Cambridge researchers Watson and Crick published their discovery of "double helix" DNA, the molecule of life, another team at the same UK university has published proof that four-stranded "quadruple helix" DNA also exists within the human genome. They hope their discovery will lead to a new generation of targeted cancer therapies that use synthetic molecules to trap the complex DNA structures and thereby stop cancer cells multiplying.

Lead investigator Shankar Balasubramanian, a professor at Cambridge University's Department of Chemistry and Cambridge Research Institute, says in a

"We are seeing links between trapping the quadruplexes with molecules and the ability to stop cells dividing, which is hugely exciting."

"The quadruple helix DNA structure may well be the key to new ways of selectively inhibiting the proliferation of cancer cells. The confirmation of its existence in human cells is a real landmark," he adds.

Balasubramanian and colleagues write about their findings in the 20 January online issue of Nature Chemistry.

From Concept to Test Tube to Living Cells

Their discovery marks the end of 10 years research to prove that four-stranded quadruple helix DNA structures, known as G-quadruplexes, also occur in living human cells.

They are called G-quadruplexes because they form in regions of DNA rich in Guanine, one of the four chemical bases or building blocks that encode genetic information (the other three are Adenine, Cytosine, and Thymine).

The team started with hypothetical computer models of the quadruplexes, then made synthetic versions in test tubes, and then proved, using fluorescent biomarkers, that the structures exist in real life in human cancer cells.

Although there is evidence that G-quadruplexes occur in single-celled organisms called ciliates, this is the first time they have been seen in human cells.

In their paper, Balasubramanian and colleagues also show that the quadruplexes are more concentrated in genes of cells that are rapidly dividing, such as cancer cells.

Balasubramanian says this suggests targeting the quadruplexes could form the basis of new personalized treatments.

To detect the quadruplexes, lead author Giulia Biffi, a researcher in Balasubramaninan's lab, made antibody proteins that bind to them.

The team were able to see "hot spots" in the genome where there were concentrations of four-stranded DNA because they tagged the antibodies with fluorescent markers.

While four-stranded DNA is spread fairly evenly through the genome of human cells and their division cycles, it appears they become more concentrated during the "s-phase" of the cell cycle. This is the point

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