Cambridge University scientists say they have seen four-stranded DNA at work in human cells for the first time.
The famous "molecule of life", which carries our genetic code, is more familiar to us as a double helix.
But researchers tell the journal
Nature Chemistry that the "quadruple helix" is also present in our cells, and in ways that might possibly relate to cancer.
They suggest that control of the structures could provide novel ways to fight the disease.
"The existence of these structures may be loaded when the
cell has a certain genotype or a certain dysfunctional state," said Prof
Shankar Balasubramanian from Cambridge's department of chemistry.
"We need to prove that; but if that is the case, targeting
them with synthetic molecules could be an interesting way of selectively
targeting those cells that have this dysfunction," he told BBC News.
Tag and track
It will be exactly 60 years ago in February that James Watson
and Francis Crick famously burst into the pub next to their Cambridge
laboratory to announce the discovery of the "secret of life".
What they had actually done was describe the way in which two
long chemical chains wound up around each other to encode the
information cells need to build and maintain our bodies.
Today, the pair's modern counterparts in the university city continue to work on DNA's complexities.
Balasubramanian's group has been pursuing a four-stranded
version of the molecule that scientists have produced in the test tube
now for a number of years.
It is called the G-quadruplex. The "G" refers to guanine, one
of the four chemical groups, or "bases", that hold DNA together and
which encode our genetic information (the others being adenine,
cytosine, and thymine).
The G-quadruplex seems to form in DNA where guanine exists in substantial quantities.
And although ciliates, relatively simple microscopic
organisms, have displayed evidence for the incidence of such DNA, the
new research is said to be the first to firmly pinpoint the quadruple
helix in human cells.
'Funny target'
The team, led by Giulia Biffi, a researcher in
Balasubramaninan's lab, produced antibody proteins that were designed
specifically to track down and bind to regions of human DNA that were
rich in the quadruplex structure. The antibodies were tagged with a
fluorescence marker so that the time and place of the structures'
emergence in the cell cycle could be noted and imaged.
This revealed the four-stranded DNA arose most frequently
during the so-called "s-phase" when a cell copies its DNA just prior to
dividing.
Prof Balasubramaninan said that was of key interest in the
study of cancers, which were usually driven by genes, or oncogenes, that
had mutated to increase DNA replication.
If the G-quadruplex could be implicated in the development of
some cancers, it might be possible, he said, to make synthetic
molecules that contained the structure and blocked the runaway cell
proliferation at the root of tumours.
"We've come a long way in 10 years, from simple ideas to
really seeing some substance in the existence and tractability of
targeting these funny structures," he told the BBC.
"I'm hoping now that the pharmaceutical companies will bring
this on to their radar and we can perhaps take a more serious look at
whether quadruplexes are indeed therapeutically viable targets."
Prof Shankar Balasubramanian in front of a painting by artist Annie Newman that represents quadruplex DNA
No comments:
Post a Comment