Scientists from Cambridge University reported in the journal Nature Chemistry on Sunday that they had found the four-stranded structure, also known as a G-quadruplex, in living human cells. More specifically, they found them in human cancer cells. If it turns out that this G-quadruplex is involved in cancer development and growth, then it would be a prime target for new drugs.
G-quadruplexes tend to form in areas of DNA with a lot of guanine, one of the building blocks of DNA that’s abbreviated G when writing out a DNA or RNA sequence. Usually, guanine binds to the nucleobase cytosine, but sometimes there are instances where four guanine bases can associate into a tetrad, or four-stranded structure.
Such structures have been seen in the test tube -- in vitro -- but never before in the natural life of a human cell, until now.
To find G-quadruplexes inside living human cancer cells, the team created antibodies that would bind to places on the genome where four-stranded structures were plentiful. Attached to the antibodies were fluorescent proteins, so the scientists could see when and where the structures emerged.
The research team from Cambridge found evidence that G-quadruplexes tend to congregate more at a point in cell division called the S-phase, which is when DNA replicates itself. The genes that fuel cancer growth are typically ones that kick DNA replication into high gear.
“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 to a halt,” senior author Shankar Balasubramanian told the university’s news service.
There are still many mysteries to be solved in the case of the 4-stranded DNA. They could have been selected for in evolution, or they could just be frustrating accidents -- like the tangles that form on strings of Christmas lights when you’re trying to pack them all away for the year.
“It’s a philosophical question as to whether they are there by design or not, but they exist, and nature has to deal with them. Maybe by targeting them we are contributing to the disruption they cause,” Balasubramanian said.
The G-quadruplex could form the basis of a targeted cancer treatment that could stop tumor growth in its tracks.
“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,” Balasubramanian told the BBC.
SOURCE: Biffi et al. “Quantitative visualization of DNA-G quadruplex structures in human cells.” Nature Chemistry published online 20 January 2013.