Quadruple Helix DNA Discovery In Human Cells Could Lead To New Cancer Therapies

Four-stranded quadruple helix DNA structures — which are known as G-quadruplexes — have been shown to exist in human cells. Scientists at the UK’s renowned Cambridge University say they have seen four-stranded DNA at work in human cells for the first time.

Most lay people will be familiar with the concept of the double helix, the two long chemical chains that wind around each other to encode the information cells needed to build and maintain human bodies.

Scientists now say the “quadruple helix” is also present in cells and could possibly relate to cancer. In addition, the discovery suggests that control of the structures could light ways to fight the disease.

Professor Shankar Balasubramanian at Cambridge’s chemistry department told BBC News.

“The existence of these structures may be loaded when the cell has a certain genotype or a certain dysfunctional state.”

He added:

“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.”

The findings are the result of 10 year plus investigation by Balasubramanian’s group to show these complex structures in living human cells  — working first from hypothetical, then computational models, to synthetic laboratory experiments, then finally, its identification in human cancer cells using fluorescent biomarkers.

Also called the G-quadruplex — the “G” refers to guanine — one of the four chemical groups that holds DNA together and encodes genetic information (along with adenine, cytosine, and thymine.)

The  G-quadruplex seems to form in DNA where guanine exists in large quantities. Translation, the four-stranded DNA arose most frequently during the so-called “s-phase” when a cell copies its DNA just prior to dividing.

Of crucial interest to the team was the study of cancers, Balasubramanian told BBC News:

“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. 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.”

The research was published in Nature Chemistry on January 20 and was funded by Cancer Research UK. It shows a clear link between four-stranded quadruplexes and the DNA replication process, which is essential for cell division and production.

By targeting quadruplexes with synthetic molecules that lure and contain these DNA structures — which prevents cells from replicating their DNA and therefore blocks cell division — scientists believe it may be possible to stop the massive cell proliferation at the root of cancer.

Interestingly, the publication of the recent findings comes in the 60th year anniversary of Cambridge researchers James Watson and Francis Crick 1953 publication of a paper describing the double helix DNA structure as the genetic code for all life, Science Daily notes.