Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists tie DNA repair to key cell signaling network

18.06.2012
Previously unknown repair byproduct could be ‘master regulator’ of many basic cell processes

University of Texas Medical Branch at Galveston researchers have found a surprising connection between a key DNA-repair process and a cellular signaling network linked to aging, heart disease, cancer and other chronic conditions. The discovery promises to open up an important new area of research — one that could ultimately yield novel treatments for a wide variety of diseases.

"This is a totally new concept — it goes against current dogma about the role of DNA repair," said UTMB professor Istvan Boldogh, senior author of a paper on the work now online in the Journal of Biological Chemistry. "We couldn't believe it ourselves, but the data convinced us."

Boldogh and his colleagues came up with the idea of a link between DNA repair and cellular signaling after a close examination of the relationship between DNA damage and cell death produced unexpected results. Conventional DNA-repair dogma holds that a cell's lifespan is determined by the amount of accumulated DNA damage it suffers — the overall corruption of genetic information stored in sequences of molecules called bases, which form the "rungs" of the DNA double helix. The cells used in Boldogh's study were especially vulnerable to damage because they lacked a key enzyme that repairs the DNA base guanine. According to dogma, this should have shortened the cells' lives; instead, they actually lived longer than expected. This made Boldogh wonder if another factor was involved in reducing the lifespan of normal cells.

"We proposed the hypothesis that instead of the accumulation of damaged guanine in DNA causing ill effects, what is significant is the release of a DNA-repair byproduct that somehow activates processes that shorten the lifespan of cells," Boldogh said.

The researchers knew just where to look to find this hypothetical repair byproduct. The majority of DNA damage is caused by ubiquitous reactive oxygen species, very chemically active molecules created as 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."

Other authors of the Journal of Biological Chemistry article include research associate Gyorgy Hajas, postdoctoral fellows Leopoldo Aguilera-Aguirre and Attila Bacsi, research scientist Muralidhar Hegde, associate professor Tapas Hazra, professors Sanjiv Sur and Sankar Mitra, Attila Bacsi of the University of Debrecen, Debrecen, Hungary, and Zsolt Radak of Semmelweis University, Budapest, Hungary. This research was supported by the National Institute of Environmental Health Sciences, the National Institute of Allergy and Infectious Disease and UTMB's National Heart Lung and Blood Institute Proteomics Center.

Jim Kelly | EurekAlert!
Further information:
http://www.utmb.edu

More articles from Life Sciences:

nachricht Topologische Quantenchemie
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

nachricht Topological Quantum Chemistry
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

Im Focus: Laser-cooled ions contribute to better understanding of friction

Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision

Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

NASA looks to solar eclipse to help understand Earth's energy system

21.07.2017 | Earth Sciences

Stanford researchers develop a new type of soft, growing robot

21.07.2017 | Power and Electrical Engineering

Vortex photons from electrons in circular motion

21.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>