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

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."


'/>"/>

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

Related biology news :

1. Stanford scientists develop gene therapy approach to grow blood vessels in ischemic limbs
2. Queens scientists seek vaccine for Pseudomonas infection
3. Scientists produce eye structures from human blood-derived stem cells
4. American Society of Plant Biologists honors early career women scientists
5. Brandeis scientists win prestigious prize for circadian rhythms research
6. Scientists discover new method of proton transfer
7. Salk scientists open new window into how cancers override cellular growth controls
8. WileyChina.com - Now Featuring Bespoke Pages for China’s Life Scientists
9. Scientists win $2 million to study new pathway in development and maintenance of lymphoma
10. UGA scientists reveal genetic mutation depicted in van Goghs sunflower paintings
11. Genetic mutation depicted in van Goghs sunflower paintings revealed by scientists
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/15/2016)... New York , March 15, 2016 ... new market report published by Transparency Market Research "Digital Door ... Trends and Forecast 2015 - 2023," the global digital door ... US$ 731.9 Mn in 2014 and is forecast to grow ... 2023. Growth of micro, small and medium enterprises (MSMEs) across ...
(Date:3/11/2016)... http://www.apimages.com ) - --> http://www.apimages.com ) - ... Images ( http://www.apimages.com ) - Germany . ... new refugee identity cards. DERMALOG will be unveiling this device, and ... Hanover next week.   --> Germany ... the new refugee identity cards. DERMALOG will be unveiling this device, ...
(Date:3/9/2016)... NEW YORK , March 9, 2016 ... current and future states of the RNA Sequencing (RNA ... in segments such as instruments, tools and reagents, data ... Analyze various segments of the RNA-Sequencing market such ... RNA-Sequencing services Identify the main factors affecting each segment ...
Breaking Biology News(10 mins):
(Date:5/23/2016)... ... 2016 , ... The need for blood donations in South Texas and across the nation is ... & Tissue Center, blood donations are on the decline. In fact, donations across the country ... percent in South Texas in the last four years alone. , There is no substitute ...
(Date:5/23/2016)... Ind. , May 23, 2016 Zimmer Biomet ... musculoskeletal healthcare, today announced that its Board of Directors has ... for the second quarter of 2016. The ... or about July 29, 2016 to stockholders of record as ... declarations of dividends are subject to approval of the Board ...
(Date:5/23/2016)... May 23, 2016 - Leading CRO,s Use ... - Frontage Implement a Single Platform to Manage End-to-end Operations ... Within the Bioanalytical lab Frontage Laboratories, a full-service contract ... and China , has selected IDBS, ... In addition to serving as the global electronic lab notebook (ELN), ...
(Date:5/23/2016)... ... May 23, 2016 , ... Foresight Institute ... announced the winners for the 2015 Foresight Institute Feynman Prizes. , These ... two categories, one for experiment and the other for theory in nanotechnology. Prof. ...
Breaking Biology Technology: