IBP Scientists Discover Left-handed Double Helix Structure in DNA Higher-order Packaging

Apr 25, 2014     Email"> PrintText Size

Chinese scientists have announced their findings on the secondary structure of chromatin, the pattern by which the human body is formed.

The new discovery of DNA's structure by Chinese scientists will provide key information for unanswered genetic questions. (Image by IBP)

On April 25, 1953, a seminal article was published in Nature magazine detailing the distinct double-helix structure of DNA, allowing humans to have a first look at how living organisms are developed from their genetic blueprint.

However, the double-helix structure of DNA seemed unlikely to be the whole story to explain the complexity of life.

"If DNA is the building block of life, the double-helix structure only allows us to know the shape of the brick that builds the mansion of the human body," says Zhou Dejin, spokesman for the Chinese Academy of Sciences.

"But there is no way yet to know the inner structure of the building, like how the bricks were constructed into walls and what is the shape of each room."

On April 25, 61 years after the discovery of DNA's structure, scientists from the academy announced their findings on the 30-nanometer chromatin fiber, the secondary structure of chromatin in Science magazine, leading us closer to the pattern the "bricks" are pieced together with.

Each human cell possesses a nucleic acid molecule that could form a 2-meter-long line. That is to say, with about 50 trillion cells, every one of us has a DNA molecule with a total length 600 times to the distance between the sun and the Earth.

The only reason we are lucky enough to maintain our average figure is that the DNA molecule folds in certain paths to become 10,000-fold shorter than its extended length.

"The DNA molecule is like a very thin filament. Two parallel filaments - the double helixes - fold and wind to form a string, and the string folds and winds into a rope. This is like the quaternary structure of chromatin - the form in which DNA exists in the nucleus of a cell," says Xu Ruiming, a professor of the Institute of Biophysics at the Chinese Academy of Science, who leads a group working on structural studies of gene expression and regulation.

The 30-nanometer chromatin fiber, the structure of which was recently posited by three research teams including Xu's, refers to the secondary structure, or the "string" formed by the double helixes of DNA molecules.

The scientists obtained the image of a 30-nanometer fiber from a cryo-electron microscopy, and for the first time in the world, found its structure - a left-handed double-helix structure in which the double helixes wind to the left, opposite to the DNA structure.

"The DNA condensation is not a random event. You can imagine that when you try to roll the wool into a ball, you will follow certain rules so it won't get tangled," Xu explains.

"The DNA condensation process is much more carefully designed - it has such special mechanisms to ensure both condensation and relaxation of the DNA, depending on which genes are necessary for cell function at any given time."

As a result, the discovery will provide key information for unanswered genetic questions, the researchers say.

"These questions include why one identical twin may have lupus while the other does not; why a fertilized egg can differentiate into more than 200 different cells; and why some drugs that act on chromatin would be effective on curing cancer," says Li Guohong, a professor at the Institute of Biophysics at the Chinese Academy of Sciences, who led a team that studied chromatin in the research.

According to Li, the 30-nanometer fiber - secondary structure of chromatin - is crucial for gene expression.

"DNA encodes the genetic information of all living organisms. However, not all the information is expressed. The selective expression of genetic information lies in the process of the relaxation of the DNA, which is decided by the way it was folded up, or the structure of the 30-nanometer fiber," he says.

Despite the international science community's acknowledgment of the function of the fiber, its structure had remained elusive over the past 30 years.

In the past, textbooks have described it as "solenoid" - an unsubstantiated hypothetical structure.

"Our discovery will definitely rewrite the textbooks," Li says.

The success in imaging the structure is thanks to the application of a technology called cryo-electron microscopy.

"Cryo-electron microscopy has been used more and more in structural biology in recent years, with its advantage on imaging the extraordinarily large size of the molecules," says Zhu Ping, a professor at the Institute of Biophysics at the Chinese Academy of Sciences, who led a team focused on 3D reconstruction and structural analysis in the research.

According to Zhu, traditional methods of imaging supramolecular structures were mainly constrained by the fact that it was extremely difficult to crystallize molecules of such large size.

The cryo-electron microscopy, however, can capture clear 3D images of the molecules without the crystallization process.

The Chinese Academy of Sciences invested 40 million yuan ($6.4 million) in a world-leading cryo - electron microscope, Titan Krios, in 2010.

The microscope, along with other cutting-edge devices, is part of a 100-million yuan protein science research platform that began in 2004 and has been open to all research teams in the Chinese Academy of Sciences.

"Of course we have international competitors who are also imaging the 30-nanometer fiber with similar devices. The reason that we are the first to succeed is that we had the right combination of talent," Zhu says.

"For example, I am good at 3-D reconstruction and structural analysis but I cannot produce a sample of 30-nanometer fiber, which professor Li Guohong is good at.

"As our three teams under the academy were working without reservation, we have advantages over researchers who were working alone." (China Daily)