Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

When Good DNA Goes Bad

13.02.2006


“Backward” DNA leads to DNA breaks associated with leukemia, study finds



When otherwise normal DNA adopts an unusual shape called Z-DNA, it can lead to the kind of genetic instability associated with cancers such as leukemia and lymphoma, according to a study by researchers at The University of Texas M. D. Anderson Cancer Center.

The study, issued in advance of the Feb. 21 edition of the Proceedings of the National Academy of Sciences, demonstrates for the first time that the oddly shaped DNA can cause DNA breaks in mammalian cells. Interestingly, these sequences prone to forming Z-DNA are often found in genetic “hot spots,” areas of DNA known to be prone to the genetic rearrangements associated with cancer. About 90 percent of patients with Burkitt’s lymphoma, for example, have DNA breaks that map to regions with the potential to form these odd DNA structures.


“Our study shows that DNA itself can act as a mutagen, resulting in genetic instability,” says Karen Vasquez, Ph.D., lead author of the study and assistant professor of carcinogenesis at M. D. Anderson’s Science Park Research Division, Smithville, Texas. “The discovery opens up a new field of inquiry into the role of DNA shape in genomic instability and cancer.”

Imagine untwisting the DNA ladder and then winding it up the other way. The result is a twisted mess with segments jutting out left and right, and the all important base pairs that hold the DNA code zigzagging in a jagged zipper shape. Scientists call this left-hand twist Z-DNA. This is a far cry from the graceful right-hand twisted helix that has become an iconic symbol of biology. It just doesn’t look right, and it doesn’t act right either, according to Vasquez. This awkward shape puts strain on the DNA, and as Vasquez and her colleagues show, can cause the DNA molecule to break completely apart.

Scientists have known for many years that DNA can take shapes other than the typical twisted ladder form, but they weren’t sure how often these alternate shapes occur inside cells.

Researchers who study these shapes had previously shown that Z-DNA can form only at certain DNA sequences because the shapes of the bases themselves contribute to Z-DNA formation. For example, the sequence CG repeated more than 14 times in a row is prone to forming Z-DNA, while the sequence AT is not as efficient at forming this structure. Analysis of the genome reveals that DNA sequences prone to forming the Z-DNA structure occur in 0.25 percent of the genome, according to Vasquez.

She and her colleagues decided to find out whether Z-DNA itself had any effect on the DNA stability. To do that, post-doctoral fellow Guliang Wang, Ph.D., made pieces of DNA designed to form the Z-DNA shape. The researchers then introduced these segments of DNA, called plasmids, into bacterial cells and human cells in the laboratory. They then broke apart the cells and examined what happens to the DNA. They found that in bacterial cells, the Z-DNA caused small deletions or insertions of one or two DNA bases. But in human cells, the introduced Z-DNA led to large-scale deletions and rearrangements of the DNA molecule.

“We discovered that bacterial cells and human cells process the Z-DNA in different ways,” she says. “We aren’t sure why, but we think that the DNA repair machinery may be involved in processing the Z-DNA structure differently in bacteria versus human cells.”

Since formation of Z-DNA is naturally occurring and can exist in the genome, the scientists next want to understand why cells can sometimes process the structure without creating double-stranded breaks. They also want to know why certain places in the genome become “hot spots” for these breaks, while other seemingly similar areas do not.

“If we could understand the players involved in this process, we might be able to prevent the generation of these breaks,” says Vasquez. “For example, if certain types of cell stress lead to breaks, we might be able to find ways to reduce those stresses and prevent breaks.”

Senior research assistant Laura Christensen also contributed to the research. The study was supported by grants from the National Cancer Institute and the National Institute of Environmental Health Sciences, as well as an Odyssey fellowship to Guliang Wang from M. D. Anderson Cancer Center.

Nancy Jensen | EurekAlert!
Further information:
http://www.mdanderson.org

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>