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 often in functions related 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.
Prof Shankar Balasubramanian in front of a painting by artist Annie Newman that represents quadruplex DNA
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 simply 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.
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 firmly 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.” Via ‘Quadruple helix’ DNA seen in human cells.
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