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Quantification of three DNA Lesions by Mass Spectrometry and Assessment of Their Levels in Tissues of Mice Exposed to Ambient Fine Particulate Matter
Published on: May 29, 2019
Repair of oxidative DNA damage--an important factor reducing cancer risk. Minireview
J Brozmanová1, A Dudás, J A Henriques
1Department of Molecular Genetics, Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovak Republic. exonbroz@savba.sk
Abstract:
Oxygen free radicals formed during normal aerobic cellular metabolism generate a variety of DNA lesions including modified bases, abasic sites and single strand breaks with blocked 3' termini. If left unrepaired, these damages may contribute to a number of degenerative processes, including cancer and aging. In most organisms, the repair of oxidative DNA lesions is supposed to be handled by the base excision repair (BER) pathway. BER is a multistep process that involves the sequential activity of several proteins, many of them were isolated and functionally characterized using the simple prokaryotic and lower eukaryotic model systems, Escherichia coli and Saccharomyces cerevisiae, respectively. As the amino acid sequence of DNA repair proteins is often well conserved from bacteria to man, our understanding of BER in higher eukaryotes drives extensively from the microbial models, namely from the yeast S. cerevisiae. Thus, results obtained on a simple yeast model are a source of new information, which can be used as a paradigm for all eukaryotic cells.
Insights
Oxidative DNA damage from metabolism can lead to aging and cancer. The base excision repair (BER) pathway, studied in yeast, is crucial for fixing these lesions in all eukaryotes.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Cellular metabolism generates oxygen free radicals, causing DNA lesions like modified bases and strand breaks.
- Unrepaired DNA damage contributes to degenerative diseases, including cancer and aging.
- The base excision repair (BER) pathway is the primary mechanism for repairing oxidative DNA damage.
Purpose of the Study:
- To highlight the conserved nature of DNA repair proteins from yeast to humans.
- To emphasize the utility of microbial models, particularly Saccharomyces cerevisiae, in understanding eukaryotic DNA repair.
Main Methods:
- Characterization of DNA repair proteins in model organisms like Escherichia coli and Saccharomyces cerevisiae.
- Comparative analysis of DNA repair protein sequences across different species.
- Extrapolation of findings from yeast to higher eukaryotic systems.
Main Results:
- DNA repair proteins show significant amino acid sequence conservation from bacteria to humans.
- Studies in yeast provide valuable insights into the mechanisms of BER in higher eukaryotes.
- Understanding BER in simple eukaryotes serves as a paradigm for complex organisms.
Conclusions:
- The yeast Saccharomyces cerevisiae is a powerful model for studying base excision repair (BER).
- Insights gained from yeast BER research are applicable to understanding DNA repair in all eukaryotic cells.
- This approach aids in comprehending the roles of DNA repair in preventing diseases like cancer and aging.
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