The Nobel Prize-winning Cambridge University duo of Watson and Crick are credited for discovering in 1953 the double helix structure of the DNA molecule, which is known for housing the chemical, genetic code (i.e. the stored biological information) of life. DNA stands for deoxyribonucleic acid, which encodes the genetic instructions of all living organisms, and it is comprised of combinations of four basic units called nucleotides. The four basic nucleotides of DNA are adenine, guanine, cytosine, and thymine. This year, 2013, marks the 60th anniversary of the groundbreaking work of Watson and Crick, and, interestingly enough, another set of Cambridge researchers have just proven that four-stranded ‘quadruple helix’ DNA structures, which they call G-quadruplexes, also exist in the human genome, especially around the building block guanine.
According to Professor Shankar Balasubramanian, who spearheaded the group research at the University of Cambridge’s Department of Chemistry and Cambridge Research Institute, “The research indicates that quadruplexes are more likely to occur in genes of cells that are rapidly dividing, such as cancer cells. For us, it strongly supports a new paradigm to be investigated – using these four-stranded structures as targets for personalised treatments in the future.”
In the past, quadruplex DNA structures had been observed to form in laboratory test tubes, and were merely dismissed as curiosities. But now Cambridge scientists have discovered that quadruplexes do in fact appear in nature. The Cambridge team first generated antibody proteins that detected then bound themselves to areas rich in quadruplex-structured DNA in the lab. Afterwards they field-tested the antibody proteins in living human cells, and when they did so, the quadruplexes were found to also exist in living human cells, particularly cancer cells.
Cancer cells are those which have spiraled out of control, leading to cell proliferation and eventual tumor growth. It is believed that genes called oncogenes have mutated in such way as to signal increased DNA replication and in turn augment cell proliferation. Because of this increase in DNA replication there is also an increased intensity in the number of quadruplex structures that appear. Researchers therefore deduce that targeting these quadruplex structures in cancer cells can become an eventual form of treatment.
Balasubramanian continues: “We have found that by trapping the quadruplex DNA with synthetic molecules we can sequester and stabilize them, providing important insights into how we might grind cell division [in cancer cells] to a halt.”
What is promising about quadruplex DNA structure research is that the scientists also discovered that these overactive oncogenes with high levels of quadruplex DNA structures tend to be more susceptible to outside interference. Balasubramanian explains further: “The possibility that particular cancer cells harboring genes with these motifs can now be targeted, and appear to be more vulnerable to interference than normal cells, is a thrilling prospect…..The ‘quadruple helix’ DNA structures 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.”
The next phase of research will thus focus on targeting these quadruplex DNA structures in tumor cells in such way as to hinder cancer growth.