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 NEIL
|Contact: Michael Baum|
National Institute of Standards and Technology (NIST)