Navigation Links
Mouse work: New insights on a fundamental DNA repair mechanism
Date:3/4/2010

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 lesionsplaces 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 organisma tailored form of E. coli designed to have a very high mutation ratehad 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.


'/>"/>

Contact: Michael Baum
michael.baum@nist.gov
301-975-2763
National Institute of Standards and Technology (NIST)
Source:Eurekalert

Related biology news :

1. Stem cells restore sight in mouse model of retinitis pigmentosa
2. Penn biologists determine microRNA activity is suppressed in mouse ovum
3. CCNY biologists identify new spiny pocket mouse species
4. Chloride increases response to pheromones and odors in mouse sensory neurons
5. New source of classical techniques for blood-based studies in the laboratory mouse
6. Caltech researchers show efficacy of gene therapy in mouse models of Huntingtons disease
7. Mouse brain rewires its neural circuits to recuperate from damaged neural function after stroke
8. Mouse model provides clues to human language development
9. Engineered pig stem cells bridge the mouse-human gap
10. Caffeic acid inhibits colitis in a mouse model -- is a drug-metabolizing gene crucial?
11. A new mouse model provides insight into genetic neurological disorders
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/31/2016)... , March 31, 2016  Genomics firm Nabsys has ... CEO, Barrett Bready , M.D., who returned to ... the original technical leadership team, including Chief Technology Officer, ... Product Development, Steve Nurnberg and Vice President of Software ... the company. Dr. Bready served as CEO ...
(Date:3/23/2016)... , March 23, 2016 ... erhöhter Sicherheit Gesichts- und Stimmerkennung mit Passwörtern ... (NASDAQ: MESG ), ein führender ... das Unternehmen mit SpeechPro zusammenarbeitet, um erstmals ... Finanzdienstleistungsbranche, wird die Möglichkeit angeboten, im Rahmen ...
(Date:3/22/2016)... Ontario , PROVO and ... Newborn Screening Ontario (NSO), which operates the ... for molecular testing, and Tute Genomics and UNIConnect, ... management technology respectively, today announced the launch of a ... next-generation sequencing (NGS) testing panel. NSO ...
Breaking Biology News(10 mins):
(Date:6/24/2016)... (PRWEB) , ... June 24, 2016 , ... Researchers at ... most commonly-identified miRNAs in people with peritoneal or pleural mesothelioma. Their findings are the ... read it now. , Diagnostic biomarkers are signposts in the blood, lung fluid ...
(Date:6/23/2016)... CAMBRIDGE, Mass. , June 23, 2016 /PRNewswire/ ... the development of novel compounds designed to target ... compound, napabucasin, has been granted Orphan Drug Designation ... in the treatment of gastric cancer, including gastroesophageal ... cancer stemness inhibitor designed to inhibit cancer stemness ...
(Date:6/23/2016)... 23, 2016 Houston Methodist Willowbrook Hospital ... Sports Association to serve as their official health ... Methodist Willowbrook will provide sponsorship support, athletic training ... association coaches, volunteers, athletes and families. ... Sports Association and to bring Houston Methodist quality ...
(Date:6/23/2016)... , June, 23, 2016  The Biodesign Challenge ... envision new ways to harness living systems and biotechnology, ... Art (MoMA) in New York City ... 130 participating students, showcased projects at MoMA,s Celeste Bartos ... Paola Antonelli , MoMA,s senior curator of architecture and ...
Breaking Biology Technology: