Featured Research

from universities, journals, and other organizations

Insight Into DNA's 'Weakest Links' May Yield Clues To Cancer Biology

Date:
March 24, 2005
Source:
Duke University Medical Center
Summary:
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.

Thomas D. Petes, Ph.D., chair of genetics and microbiology.
Credit: Photo courtesy of Duke University Medical Center

Durham, N.C. – 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.


Story Source:

The above story is based on materials provided by Duke University Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

Duke University Medical Center. "Insight Into DNA's 'Weakest Links' May Yield Clues To Cancer Biology." ScienceDaily. ScienceDaily, 24 March 2005. <www.sciencedaily.com/releases/2005/03/050323131423.htm>.
Duke University Medical Center. (2005, March 24). Insight Into DNA's 'Weakest Links' May Yield Clues To Cancer Biology. ScienceDaily. Retrieved August 21, 2014 from www.sciencedaily.com/releases/2005/03/050323131423.htm
Duke University Medical Center. "Insight Into DNA's 'Weakest Links' May Yield Clues To Cancer Biology." ScienceDaily. www.sciencedaily.com/releases/2005/03/050323131423.htm (accessed August 21, 2014).

Share This




More Health & Medicine News

Thursday, August 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Possible Ebola Patient in Isolation at California Hospital

Possible Ebola Patient in Isolation at California Hospital

Reuters - US Online Video (Aug. 20, 2014) — A patient who may have been exposed to the Ebola virus is in isolation at the Kaiser Permanente South Sacramento Medical Center. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Raw: World's Oldest Man Lives in Japan

Raw: World's Oldest Man Lives in Japan

AP (Aug. 20, 2014) — A 111-year-old Japanese was certified as the world's oldest man by Guinness World Records on Wednesday. Sakari Momoi, a native of Fukushima in northern Japan, was given a certificate at a hospital in Tokyo. (Aug. 20) Video provided by AP
Powered by NewsLook.com
Do More Wedding Guests Make A Happier Marriage?

Do More Wedding Guests Make A Happier Marriage?

Newsy (Aug. 20, 2014) — A new study found couples who had at least 150 guests at their weddings were more likely to report being happy in their marriages. Video provided by Newsy
Powered by NewsLook.com
Ebola-Hit Sierra Leone's Freetown a City on Edge

Ebola-Hit Sierra Leone's Freetown a City on Edge

AFP (Aug. 19, 2014) — Residents of Sierra Leone's capital voice their fears as the Ebola virus sweeps through west Africa. Duration: 00:56 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins