Quadruple helix' DNA seen in human cells

A representation of the four-stranded structure (L) and fluorescent markers reveal its presence inside cells (R) A representation of the four-stranded structure (L) with fluorescent markers revealing its presence inside cells (R)

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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 in ways that might possibly relate 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.
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 simple 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.
'Funny target' 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 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."
Prof Shankar Balasubramanian Prof Shankar Balasubramanian in front of a painting by artist Annie Newman that represents quadruplex DNA

Science

[i say wrong science]

In space, a room that can be folded like a shirt


NORTH LAS VEGAS: An inflatable space pod to be attached to the International Space Station in a couple of years will be like no other piece of the station. Instead of metal, its walls will be made of floppy cloth, making it easier to launch (and then inflate).

Nasa said on Wednesday that it had signed a $17.8 million contract with Bigelow Aerospace to build the module, which could reach the space station as soon as 2015. That is a bargain-basement price compared with most equipment the US and other countries send into space, and the Bigelow agreement could serve as a model for how Nasa puts together missions at lower costs by using a Kmart strategy: buying off-theshelf pieces instead of developing its own designs.

"This programme starts a relationship that we think, and we hope, is going to be meaningful between Nasa and ourselves," Robert T Bigelow, the chief executive of Bigelow Aerospace, said at a news conference here at the company's headquarters.

Low-Earth orbit, he said, is the "first target," but larger modules could be used for stations in deep space or for habitats on the Moon. "We have ambitions to get to the Moon someday, to have a base there," Bigelow said.

The fold-up , blow-up approach solves the conundrum of how to build something voluminous that can be packed into the narrow payload confines of a rocket. The soft sides of the module , called the Bigelow Expandable Activity Module, or Beam, will allow it to be scrunched like a T-shirt in a suitcase.

At the space station, it will be attached to an air lock and then inflated like a balloon and expanded by a factor of 10 to its full size — about 13 feet long and 10 feet in diameter, with about 560 cubic feet of space inside.

At least initially, it will remain empty as Nasa gathers data about its characteristics, including temperature and protection against micrometeorites.

The balloonlike structure is carefully designed not to pop. The fabric walls will consist of several layers including Vectran , a bullet-resistant material. Even if punctured by a highspeed meteorite, the fabric does not tear. A hole in a metal structure in space, by comparison, can cause explosive decompression as air rushes out.

When the Beam module reaches the space station, astronauts might go to it to seek solitude: engineers expect it will be the quietest spot there. The fabric walls absorb sound vibrations instead of transmitting them.

Beam revives a concept that Nasa developed more than a decade ago for an inflatable four-story crew quarters on the space station. Congress halted the work as the station's construction costs grew sharply.

Bigelow licensed the technology from Nasa and set up his factory in North Las Vegas, investing over $250 million of his own money. The company has already launched two unmanned prototypes into orbit, showing that they can remain inflated for years.