But now researchers have found that human DNA can naturally wrap
itself into a different shape – a quadruple helix – in a breakthrough
that could point the way to new cancer treatments.
The new structure, which is composed of four strands wrapped around
each other, was confirmed by scientists from Cambridge University – the
place where Crick and Watson made their famous discovery.
The quadruple DNA helix appears to be more common in cells that are
rapidly dividing, indicating that it could be important in determining
whether or not a cell becomes cancerous.
Professor Shankar Balasubramanian, who led the study published in the
journal Nature Genetics, said: “It is quite a distinct structure to the
double helix. It’s a beautiful four-stranded helix that we know little
about, but we are convinced it exists naturally.
“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.
“We are seeing links between trapping the quadruplexes with molecules
and the ability to stop cells dividing, which is hugely exciting. The
research indicates that quadruplexes are more likely to occur in genes
of cells that are rapidly dividing, such as cancer cells.”
The DNA double helix was one of the greatest discoveries in science
because it laid the foundations for understanding how genetic
information is passed from one generation to the next, and how this
information controls the biochemistry of the body.
Although scientists had known that DNA could form other unusual
structures in the laboratory under artificial conditions, this is the
first time that scientists have been able to show that it also forms a
quadruple helix within living human cells.
Dr Julie Sharp, the senior science information officer at Cancer
Research UK, which helped fund the work, said: “It’s been 60 years since
its structure was solved but work like this shows us that the story of
DNA continues to twist and turn
This research further highlights the potential for exploiting these
unusual DNA structures to beat cancer. The next part of the pipeline is
to figure out how to target them in tumour cells.”
The huge DNA molecule contains all the genetic information necessary
to make a human being, encoded in the sequence of four chemical units or
“bases”, abbreviated as C, G, A and T, that make up the primary
molecular structure of the chromosomes.
Professor Balasubramanian and his colleagues discovered that when
there is a high proportion of the guanine base, the G unit, the double
helix breaks down into the quadruple form, which forms a tight knot
within the DNA molecule.
When the scientists used small drug-like molecules to trap these
quadruplex structures, they discovered that they could interfere with
the process of cell division, suggesting that the quad helix is somehow
involved in the replication of cells – and hence the uncontrolled
replication seen in cancers.
“We have found that by trapping the quadruplex DNA with synthetic
molecules we can sequester and stabilise them, providing important
insights into how we might grind cell division to a halt,” Professor
Balasubramanian said. “There is a lot we don’t know yet. One thought is
that these quadruplex structures might be a bit of a nuisance during DNA
replication, like knots or tangles that form… The possibility that
particular cells harbouring genes with these motifs can now be targeted,
and appear to be more vulnerable to interference than normal cells, is a
thrilling prospect.”
Shankar Balasubramanian was born in Madras (now Chennai), India, in
1966 and came to Britain with his parents a year later. He grew up just
outside Runcorn in Cheshire where he attended local schools.
He graduated from Cambridge University in 1988 and stayed on to do
his PhD. He is now the Herchel Smith Professor of Medicinal Chemistry
and also works at the Cambridge Research Institute – a collaboration
between the university and the charity Cancer Research UK. He was
elected a Fellow of the Royal Society last year.
