Recently a study has found that forces from external environment and oxidation may be the greatest threat to an organism's ability to repair damage to its own DNA. The results are published in the journal of the Proceedings of the National Academy of Sciences, which also publishes some other studies on Recombinant protein. The results are based on the first comprehensive, whole genome analysis of spontaneous mutation in the bacterium Escherichia coli.
"Our study investigated 11 DNA repair pathways previously identified as resulting in spontaneous mutations," said Foster, a professor in the IU Bloomington College of Arts and Sciences' Department of Biology. "The striking result was that only loss of the ability to prevent or repair oxidative DNA damage significantly impacted mutation rates. ... All other forms of DNA damage arising within the organism did not disturb the overall accuracy of DNA replication in normally growing cells.
"These results suggest that DNA repair pathways may exist primarily to defend against externally induced damage to the genome," she said. Foster's lab and her work concentrates on DNA mutagenesis and repair. E. coli is a bacterium discovered in mammalian digestive tracts. It's more known as a source of food poisoning. It was chosen for the research because the biological pathways that control DNA repair have changed little as more complex organisms evolved, increasing the chances that the study's results are applicable to higher forms of life, including humans.
Foster's lab created the world's most comprehensive picture of genetic mutation in the species by tracing changes in E. coli's complete genome over the course of 200,000 generations. The IU team concentrated on 11 processes identified in other studies as causing mutation when deactivated, to focus their investigation on the relative importance of the pathways that repair DNA damage to genetic mutation. The pathways were isolated using 11 different strains of E. coli, each defective for one of the specific pathways.
After investigation, the DNA repair pathways under investigation fell into three broad categories. They were the activities of error-prone DNA polymerases, repair of internally induced DNA damage, including oxidation, and repair of DNA damage due to external agents. Each pathway is more or less specific for a given type of DNA damage. External agents such as radiation, chemical compounds and platinum-based compounds, are forces that affect DNA. And internal agents that damage DNA are produced by the body's own normal processes. Oxidation occurs in the body as a result of metabolic processes that use oxygen, creating molecules known as "free radicals" that steal electrons from other molecules in the body, causing damage. Many types of cancer and even aging have been linked to DNA oxidation.
The IU scientists used whole genome sequencing to catalog the specific genetic changes that resulted from loss of each repair pathway. Foster said that, surprisingly, the IU team found that none of the pathways resulted in mutations except the ones that deal with damage from oxidation. This means that the other types of damage—from either internal or external causes—are not a great threat to normally growing cells.
These pathways may be important, however, when cells are exposed to external agents or other forms of stress. The more complete picture of genetic mutation—made possible by the IU team's previous documentation of the bacterium's evolution over 200,000 generations—is likely responsible for the difference in the study's results compared to previous research implicating all 11 DNA repair pathways in genetic mutation, Foster said.
"Previous studies on mutational processes have relied on reporter genes"—single genes that signal larger changes across the genome—"to detect mutations, and these may not be representative of the genome as a whole," she said. "While reporter genes can reveal important mutational processes that occur at particular spots in the DNA, when the whole genome is the target, these localized errors don't appear to contribute to overall mutation."
Foster's next step is investigate DNA repair functions in cells under stress, which may provide a more complete model for mutational processes in living human cells existing in different states and environments all over the body. The experiments and research can help scientists understand more about DNA repair in our body and the importance of them. Flarebio offers good-quality recombinant proteins like recombinant LARGE at good prices.
