Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mouse Work: New Insights on a Fundamental DNA Repair Mechanism

04.03.2010
Adding a new link to our understanding of the complex chain of chemistry that keeps living cells alive, a team of researchers from the University of Vermont (UVM), the University of Utah, Vanderbilt University and the National Institute of Standards and Technology (NIST) has demonstrated for the first time the specific activity of the protein NEIL3, one of a group responsible for maintaining the integrity of DNA in humans and other mammals. Their work reported last week* sheds new light on a potentially important source of harmful DNA mutations.

Since it first was identified about eight years ago, NEIL3 has been believed to be a basic DNA-maintenance enzyme of a type called a glycosylase. These proteins patrol the long, twisted strands of DNA looking for lesions—places where one of the four DNA bases has been damaged by radiation or chemical activity. They cut the damaged bases free from the DNA backbone, kicking off follow-on mechanisms that link in the proper undamaged base. The process is critical to cell health, says NIST biochemist and Senior Research Fellow Miral Dizdaroglu, “DNA is damaged all the time. About one to two percent of oxygen in the body becomes toxic in cells, for example, creating free radicals that damage DNA. Without these DNA repair mechanisms there wouldn’t be any life on this planet, really.”

The glycosylases seem to be highly specific; each responds to only a few unique cases of the many potential DNA base lesions. Figuring out exactly which ones can be challenging. NEIL3 and its kin NEIL1 and NEIL2 are mammalian versions of an enzyme found in the bacterium E. coli, which first was identified in work at UVM. The lesion targets of NEIL1 and NEIL2 have been known for some time, but NEIL3, a much more complicated protein twice the size of the others, had resisted several attempts to purify it and determine just what it does. In a significant advance, a research team at UVM managed to clone the house mouse version of NEIL3 (99 percent identical to the human variant), and then prepare a truncated version of it that was small enough to dissolve in solution for analysis but large enough to retain the portion of the protein that recognizes and excises DNA lesions.

Using a technique they developed for rapidly analyzing such enzymes, NIST researchers Dizdaroglu and Pawel Jaruga mixed the modified protein with sample DNA that had been irradiated to produce large numbers of random base lesions. Because glycosylases work by snipping off damaged bases, a highly sensitive analysis of the solution after the DNA has been removed can reveal just which lesions are attacked by the enzyme, and with what efficiency. The NIST results closely matched independent tests by others in the team that match the enzyme against short lengths of DNA-like strands with a single specific target lesion.

In addition to finally confirming the glycosylase nature of NEIL3, says UVM team leader Susan Wallace, tests of the enzyme in a living organism—a tailored form of E. coli designed to have a very high mutation rate—had an unexpected bonus. Measurements at NIST showed that NEIL3 is extremely effective at snipping out a particular type of lesion called FapyGua** and seems to dramatically reduce mutations in the bacterium, a result that points both to the effectiveness of NEIL3 and the potentially important role of FapyGua in causing dangerous mutations in DNA.

* M. Liu, V. Bandaru, J.P. Bond, P. Jaruga, X. Zhao, P.P. Christov, C.J. Burrows, C.J. Rizzo, M. Dizdaroglu and S.S. Wallace. The mouse ortholog of NEIL3 is a functional DNA glycosylase in vitro and in vivo. Proc. Natl. Acad. Sci. USA, Early Edition, Published online before print Feb. 25, 2010, doi:10.1073/pnas.0908307107.

** 2,6-diamino-4-hydroxy-5-formamidopyrimidine

Michael Baum, michael.baum@nist.gov, (301) 975-2763

Michael Baum | Newswise Science News
Further information:
http://www.nist.gov

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

Multiregional brain on a chip

16.01.2017 | Power and Electrical Engineering

New technology enables 5-D imaging in live animals, humans

16.01.2017 | Information Technology

Researchers develop environmentally friendly soy air filter

16.01.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>