EAST LANSING, Mich. – In the quest to repair damaged DNA – a process believed crucial in combating ailments ranging from cancer to aging – antioxidant has been the Holy Grail. But findings published this week in Nature suggest oxidation isn't always the enemy. Scientists at Michigan State University, along with colleagues in England, have uncloaked a mechanism that uses oxygen to repair DNA – until now an unlikely part of the restorative recipe. Their work is published in the Sept. 12 issue of the British science journal Nature.
"This offers possibilities to anyone working in the DNA repair field who likely hasn't considered oxygenation before," said Robert Hausinger, an MSU microbiology and biochemistry professor. "The field has been so focused against it."
Hausinger, his doctoral student Timothy Henshaw and colleagues from the Cancer Research UK London Research Institute in Hertfordshire, England, figured out how an enzyme in E. coli bacteria handily repairs DNA that suffer a common type of damage. In particular, one peril that can befall DNA is a process called methylation, in which a methyl group latches on to the strand, threatening mutation.
Enzymes are the superheroes of the DNA world, rushing to fix the strands that are the building blocks of all life. Some proteins are effective at knocking off the offending methyl group, but die in the process. This "suicide repair" means the enzymes are only good for one fight. Others get rid of the methyl group along with one of the rungs of the DNA ladder, leaving a big hole in the DNA strand that must be repaired.
Hausinger and Henshaw focused their attention on the protein AlkB. Researchers have known AlkB for years, but didn't understand how the enzyme worked its repair magic. The MSU team discovered it neatly performs a chemical mambo that uses iron and oxygen to burn off the renegade methyl group. What's left at the end of oxidation is formaldehyde.
The British part of the team – Sarah Trewick, Tomas Lindahl and Barbara Sedgwick, confirmed repair of the DNA, allowing survival of the cells.
"It's sweet," Hausinger said. "It burns off the methylation and doesn't kill itself in the process. It can work on one lesion and then move on and do it again."
Methylation isn't always bad, Hausinger said, but rather is an important natural process that also occurs in human DNA. However, the process is part of DNA damage associated with some environmental toxins, as well as in cancer and maladies of aging.
"Although we worked with AlkB from E. coli, the enzyme is actually found in a wide variety of organisms, including humans," Henshaw said. "Since it’s so widely conserved, it’s likely to have a role in some crucial biological functions."
The U.S. National Institutes of Health funded the research.