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Scientists tie DNA repair to key cell signaling network
Date:6/15/2012

byproducts of respiration. When DNA meets reactive oxygen species, one of the most common results is the transformation of the DNA base guanine into a molecule called 8-oxoguanine, which can produce mutations in genes.

To protect the integrity of the genetic code, cells remove 8-oxoguanine from their DNA with a repair enzyme called OGG1. OGG1 does its job by attaching to a damaged base, cutting it free from the DNA molecule, and then releasing it. Boldogh and his collaborators found that their key byproduct was being produced just after this repair process was completed. Analyzing test-tube, cell-culture and mouse experimental data, they realized that immediately after being released by OGG1, 8-oxoguanine reunites with the repair enzyme, attaching at a bonding site different from the one used previously. And the resulting 8-oxoguanine-OGG1 complex, they found, has the ability to activate the powerful Ras signaling pathways, some of the most important biochemical networks in the cell.

"Ras family proteins are involved in almost every cell function: metabolism, activation of genes, growth signals, inflammation signals, apoptosis," Boldogh said. "Because it activates Ras pathways, the release of 8-oxoguanine in DNA base repair could be a master regulator of many very basic processes."

According to Boldogh, learning to control this "master regulator," could result in profound consequences for biomedical science and human health. "The ability to regulate 8-oxoguanine excision may give us the ability to prevent the inflammation that's key to a number of chronic diseases arthritis, atherosclerosis, Alzheimer's and others," he said. "We believe it may even enable us to extend lifespan, or at least healthy lifespan, which would be a very big achievement. Possibilities like that make us believe that this discovery is going to be very significant."


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Contact: Jim Kelly
jpkelly@utmb.edu
409-772-8791
University of Texas Medical Branch at Galveston
Source:Eurekalert

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