Featured Research

from universities, journals, and other organizations

Nature's elegant solution to repairing DNA in cancer, other conditions

Date:
April 21, 2011
Source:
Duke University Medical Center
Summary:
A major discovery about an enzyme's structure has opened a window on understanding DNA repair. Scientists have determined the structure of a nuclease that will help scientists to understand several DNA repair pathways, a welcome development for cancer research.

A major discovery about an enzyme's structure has opened a window on understanding DNA repair. Scientists at Duke University Medical Center have determined the structure of a nuclease that will help scientists to understand several DNA repair pathways, a welcome development for cancer research.

Related Articles


DNA repair pathways are very important in the context of cancer biology and aging, but the tools the cell uses to do those repairs are not well understood.

"Until we saw the structure using X-ray crystallography, we didn't understand how it could recognize so many unusual DNA structures," said senior author Lorena Beese, Ph.D., James B. Duke Professor of Biochemistry. "The relative arrangement of the binding sites and of the active site itself for this enzyme is important for recognition during the repair process, and I don't think we could have imagined how it came together."

The study appears in this week's issue of Cell journal.

"We present the first structural information about these nucleases in humans, and that information is important for DNA substrate recognition and enzymatic mechanism," Beese said. "The discovery is important for understanding the mismatch repair pathway, and more generally, it will help us understand other pathways as well."

If mismatch repairs are not completed properly, this deficiency can have profound effects on human health, including genes that mutate spontaneously, forms of colorectal cancer, and the development of an estimated 15-25 percent of sporadic tumors, the authors noted.

"Scientists have been interested in obtaining a detailed picture of where the atoms are in this protein for a long time. We were able to determine the structure, because we put together the right experiments at the right time -- good protein expression, good purification, and fortunately when we got crystals we had the right team to solve the structure and do the biochemical experiments," Beese said. "This was truly a team effort."

The next step is to study complexes of this molecule with other proteins in the repair pathway. "By understanding the interactions between proteins, we will get more insight into how it works and how the activities are regulated," Beese said. "In terms of future therapeutic strategies, these interfaces present exciting targets for new drugs."

Also to be published in the April 14 issue of Cell, a team lead by John Tainer at the Lawrence Berkeley labs reports that another nuclease in a related pathway has the same structural arrangements.

"It's remarkable how nature has solved complex topological puzzles in DNA substrate recognition with such elegant simplicity," Beese said.

Other authors include Jillian Orans , Elizabeth A. McSweeney, Ravi R. Iyer, Michael A. Hast, Homme W. Hellinga, and Paul Modrich, all from the Duke Department of Biochemistry.

This work was supported by National Institutes of Health grants, including the Structural Biology of DNA Repair (SBDR) program project grant from the National Cancer Institute and to Dr. Modrich support from the Howard Hughes Medical Institute.


Story Source:

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


Journal Reference:

  1. Jillian Orans, Elizabeth A. McSweeney, Ravi R. Iyer, Michael A. Hast, Homme W. Hellinga, Paul Modrich, Lorena S. Beese. Structures of Human Exonuclease 1 DNA Complexes Suggest a Unified Mechanism for Nuclease Family. Cell, 2011; 145 (2): 212 DOI: 10.1016/j.cell.2011.03.005

Cite This Page:

Duke University Medical Center. "Nature's elegant solution to repairing DNA in cancer, other conditions." ScienceDaily. ScienceDaily, 21 April 2011. <www.sciencedaily.com/releases/2011/04/110420112322.htm>.
Duke University Medical Center. (2011, April 21). Nature's elegant solution to repairing DNA in cancer, other conditions. ScienceDaily. Retrieved November 29, 2014 from www.sciencedaily.com/releases/2011/04/110420112322.htm
Duke University Medical Center. "Nature's elegant solution to repairing DNA in cancer, other conditions." ScienceDaily. www.sciencedaily.com/releases/2011/04/110420112322.htm (accessed November 29, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, November 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Rural India's Low-Cost Sanitary Pad Revolution

Rural India's Low-Cost Sanitary Pad Revolution

AFP (Nov. 28, 2014) — One man hopes his invention -– a machine that produces cheap sanitary pads –- will help empower Indian women. Duration: 01:51 Video provided by AFP
Powered by NewsLook.com
Research on Bats Could Help Develop Drugs Against Ebola

Research on Bats Could Help Develop Drugs Against Ebola

AFP (Nov. 28, 2014) — In Africa's only biosafety level 4 laboratory, scientists have been carrying out experiments on bats to understand how virus like Ebola are being transmitted, and how some of them resist to it. Duration: 01:18 Video provided by AFP
Powered by NewsLook.com
WHO Says Male Ebola Survivors Should Abstain From Sex

WHO Says Male Ebola Survivors Should Abstain From Sex

Newsy (Nov. 28, 2014) — WHO cites four studies that say Ebola can still be detected in semen up to 82 days after the onset of symptoms. Video provided by Newsy
Powered by NewsLook.com
Ebola Leaves Orphans Alone in Sierra Leone

Ebola Leaves Orphans Alone in Sierra Leone

AFP (Nov. 27, 2014) — The Ebola epidemic sweeping Sierra Leone is having a profound effect on the country's children, many of whom have been left without any family members to support them. Duration: 01:02 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:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

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