Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Insight into DNA’s "Weakest Links" May Yield Clues to Cancer Biology

11.03.2005


The chromosomes of mammals, including humans, contain regions that are particularly prone to breaking under conditions of stress and in cancer. Now, new research by geneticists at Duke University Medical Center finds that yeast cells also contain such weak links in DNA and begins to reveal the molecular characteristics of these links that might help to explain them.



The findings, published in the March 11, 2005, issue of Cell, suggest that yeast may offer a useful model system for studying the fundamental properties of so-called DNA fragile sites, providing new insight into the chromosomal instability found in cancer cells, said the researchers. "If you look at solid tumors in humans, you see that the chromosomes of cancer cells exhibit incredible instability," said Thomas Petes, Ph.D., chair of genetics and microbiology at Duke. "Now, we have been able to mimic some of that instability in yeast cells and can begin to ask whether there is anything special that defines those places where chromosomes tend to break."

Organisms normally exhibit extremely low rates of mutation and chromosomal rearrangements. Conditions that elevate genomic instability lead to an increase in cell death and, in some cases, an increased incidence of cancer, Petes said. Earlier work by other researchers had shown that mammalian chromosomes break at particular sites under certain types of stress or upon exposure to particular drugs, he said. Evidence has suggested that chromosomes break when DNA replication – the process by which DNA copies itself before cell division – slows or stalls. However, the DNA characteristics that make particular sites vulnerable to breakage had remained unclear, he said.


The researchers slowed DNA replication in yeast cells by reducing the availability of one form of DNA polymerase, which are enzymes critical in DNA duplication. Yeast with abnormally low levels of DNA polymerase exhibited higher frequencies of chromosomal loss and aberrations than normal, resulting when broken chromosomes re-joined with others to form novel arrangements, the researchers reported. Through further examination of breakpoints in a small region of one chromosome, the researchers found that the fragile sites occurred at locations along the DNA containing "retrotransposons" called Ty elements. Retrotransposons are mobile gene segments that duplicate themselves and insert the new copies back into other sites in the genome.

The most common breakpoint involved two Ty elements in an inverted, head-to-head orientation, they reported. That finding led the researchers to suggest one possible mechanism for chromosomal breaks and rearrangements. A delay in DNA synthesis leads to an increase in single-stranded DNA, the researchers explained. While DNA is in a single-stranded form, multiple copies of retrotransposons are more likely to interact, forming a kink in the DNA. Rearrangements may occur when those kinks are improperly excised and repaired by rejoining with retrotransposons on other chromosomes. "The current findings offer the first indication that yeast have fragile sites," said Francene Lemoine, Ph.D., of Duke, first author of the study. "The finding will allow us to develop a simple model to study fragile sites in a way that can’t be done in more complex organisms."

The findings suggest that mammalian and yeast fragile sites may have common features, an indication that a common mechanism may underlie their occurrence, Petes said. Fragile sites in mammalian cells tend to duplicate late and also include sequences prone to forming kinks, or hairpin structures, like those observed in yeast. "The findings may ultimately help us better understand what goes wrong in cancer cells, an important step in developing a better plan of attack against the disease," Petes added.

Collaborators on the study include Natasha Degtyareva, of Emory University, and Kirill Lobachev, of the Georgia Institute of Technology. The work was supported by the National Institutes of Health, the National Cancer Institute and the National Science Foundation.

Kendall Morgan | EurekAlert!
Further information:
http://www.duke.edu

More articles from Life Sciences:

nachricht Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

Im Focus: Newly proposed reference datasets improve weather satellite data quality

UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration

"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...

Im Focus: Repairing defects in fiber-reinforced plastics more efficiently

Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.

Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Solar Collectors from Ultra-High Performance Concrete Combine Energy Efficiency and Aesthetics

16.01.2017 | Trade Fair News

3D scans for the automotive industry

16.01.2017 | Automotive Engineering

Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs

16.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>