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Removing DNA repair gene causes metabolic syndrome

l repair enzyme and immediately began constructing the repair-deficient mice.

"If you have oxidative stress inside the cell, then the bases in the DNA can become damaged, and the responsibility of this whole group of enzymes is essentially to monitor the entire genome, looking for genomic bases that have been oxidatively damaged," Lloyd explained. "They have the responsibility of then removing the damaged bases, which initiates a process by which the cell puts in a normal piece of DNA where the damaged DNA was. This happens every second of your life."

After breeding several generations of NEIL1 "knock-out" mice, Lloyd's colleague and the study's lead author, Vladimir Vartanian, Ph.D., found that the mice lacking the enzyme reached weights of between 45 and 52 grams at age 7 months, while normal mice weighed in at only 28 grams. They also were extremely lethargic, their hair was turning gray, and some were even going bald.

And there were gender differences. "The NEIL1 knock-out males throughout all of our studies usually show a more severe form of the disease and earlier onset of the disease than the females. We have consistently seen this," Lloyd said. "The female has disease, but it's not nearly to the same severity."

Previous studies have suggested that because there are increased levels of NEIL1 during the synthesis or "S" phase of the cell division cycle, during which DNA is replicated before the cell actually divides, NEIL1 is important to replication-associated DNA repair. In addition, NEIL1 has been shown to be localized in both the cell's nucleus and its power plant, the mitochondria, pointing to its likely involvement in the overall maintenance of the genome's stability. Other investigators in the field have discovered that NEIL1 may be important in the repair of actively transcribed genes.

This means mutations in the NEIL1 gene, or the gene's absence altogether, could have a catastrophic effect on the body's ability
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Source:Oregon Health & Science University


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