January 21st, 2013 by Michael Ricciardi
Most all DNA — the DNA we all learned about in school — has two strands of genetic material, each spiraling about the other in what is referred to as a double helix. But apparently, our cells also have four-stranded DNA as well…and, the presence of this “funny” DNA may be related to the development of cancer which often results when DNA repair mechanism malfunction or go awry.
“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 [source: BBC interview].
So far, this hypothesis is unproven, and awaits validation, but if the presence of this form of DNA can be shown to promote the dysfunctional state of the cell, then targeting it with specially designed synthetic molecules may be possible. The scientists speculate that controlling the quadruple structured DNA might provide a way to combat the disease.
Life Imitates Lab Work
Balasubramanian’s lab has been trying to locate an in vivo (i.e., in living cells) version of the four-stranded DNA that actually has been previously produced in vitro (in the laboratory) for some years now.
This synthetic form of DNA is called G-quadruplex.The ‘G’ stands for guanine, which is one of the four nucleotide bases (i.e., the “chemical building blocks”) of DNA (the other three being cytosine, adenine, and thymine) designated by the letters C, A, and T, respectively.
Intriguingly, wherever guanine exists in large quantities, the G-quadruplexes seem to form in the cell’s DNA.
Previous research has found evidence of these four-stranded complexes in organisms called ciliates (a type of protozoan), this new research represents the first time this form of DNA has been found in human cells.
How to Find Quadruplex DNA
The Cambridge research team, led by Giulia Biffi,first produced antibody proteins that were engineered to target and then bind to regions of DNA in which the quadruplex structures were known to be plentiful. The antibodies had a fluorescent marker attached to them to alert the team when (and where) in the cell cycle the quadruplex structures emerged. The structures could then be imaged.
The technique revealed that the quadruplex DNA structures tended to emerge during the cell’s “s phase” which occurs when the cell duplicates its DNA just prior to cell division (mitosis).
How the Discovery May Help the Fight Against Cancer
Many cancers are typically driven by cancer-causing genes called oncogenes (yes, our DNA actually contains genes that cause cancer) which can mutate and increase DNA replication.
So, if the G-quadruplex can be shown to be at work when a cell changes from normal to cancerous, it might be possible to target the quadruplexes with synthetic binding molecules — called ligands — and block the run-away cell proliferation that is the foundation of tumorigenesis.
According to the published paper abstract:
Together these findings provide substantive evidence for the formation of G-quadruplex structures in the genome of mammalian cells and corroborate the application of stabilizing ligands in a cellular context to target G-quadruplexes and intervene with their function.
Professor Balasubramanian refers to these strange complexes as “funny structures” and acknowledges the progress made over the past ten years. He has big hopes that this current research will lead to a breakthrough in cancer treatment.
“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.” [quote source]
Results of the research were published January 20, 2013 in the journal Nature Chemistry under the title ‘Quantitative visualization of DNA G-quadruplex structures in human cells’
Some source material for this post came from the BBC News article ‘Quadruple helix’ DNA seen in human cells’ by Jonathan Amos
Top image – A representation of the four-stranded structure (L) with fluorescent markers revealing its presence inside cells (R); credit J-P. Rodriguez and G. Biffi via the BBC News – Science and Environment website.
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