DNA damage-induced reactive oxygen species (ROS) stress response in Saccharomyces cerevisiae

Cells are exposed to both endogenous and exogenous sources of reactive oxygen species (ROS). At high levels, ROS can lead to impaired physiological function through cellular damage of DNA, proteins, lipids, and other macromolecules, which can lead to certain human pathologies including cancers, neur...

Full description

Saved in:
Bibliographic Details
Published in:Free radical biology & medicine 2008-10, Vol.45 (8), p.1167-1177
Main Authors: Rowe, Lori A., Degtyareva, Natalya, Doetsch, Paul W.
Format: Article
Language:English
Subjects:
DNA damage
DNA Damage - physiology
DNA repair
DNA Repair - genetics
Genotoxic stress
Oxidative Stress - physiology
Oxidative stress response
Protein Transport - physiology
Reactive oxygen species
Reactive Oxygen Species - metabolism
Saccharomyces cerevisiae
Saccharomyces cerevisiae - physiology
Saccharomyces cerevisiae Proteins - metabolism
Transcription Factors - metabolism
Yap1 transcription factor
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Cells are exposed to both endogenous and exogenous sources of reactive oxygen species (ROS). At high levels, ROS can lead to impaired physiological function through cellular damage of DNA, proteins, lipids, and other macromolecules, which can lead to certain human pathologies including cancers, neurodegenerative disorders, and cardiovascular disease, as well as aging. We have employed Saccharomyces cerevisiae as a model system to examine the levels and types of ROS that are produced in response to DNA damage in isogenic strains with different DNA repair capacities. We find that when DNA damage is introduced into cells from exogenous or endogenous sources there is an increase in the amount of intracellular ROS which is not directly related to cell death. We have examined the spectrum of ROS in order to elucidate its role in the cellular response to DNA damage. As an independent verification of the DNA damage-induced ROS response, we show that a major activator of the oxidative stress response, Yap1, relocalizes to the nucleus following exposure to the DNA-alkylating agent methyl methanesulfonate. Our results indicate that the DNA damage-induced increase in intracellular ROS levels is a generalized stress response that is likely to function in various signaling pathways.
ISSN:0891-5849
1873-4596
DOI:10.1016/j.freeradbiomed.2008.07.018