Editors' ChoiceReactive Oxygen Species

Yeast Networks That Combat Oxygen Radicals

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Science's STKE  08 Mar 2005:
Vol. 2005, Issue 274, pp. tw90
DOI: 10.1126/stke.2742005tw90

Reactive oxygen species (ROS) have been linked to cancer and aging. These molecules, including superoxide and hydroxyl radicals and hydrogen peroxide, arise from both intracellular and extracellular sources. Their effects on DNA are broad, causing mutations through DNA breaks, defects in recombination, and gross chromosomal rearrangements (GCRs). Antioxidative enzymes are often engaged to maintain a normal cellular redox state. Huang and Kolodner have further found that if endogenous ROS increases, specific DNA repair and cell division cycle checkpoint mechanisms are engaged to prevent the deleterious effects of oxygen radicals. In the yeast Saccharomyces cerevisiae, the peroxidase TSA1 protects genomic stability, and its absence increases mutation rates. In strains that lack the tsa1 gene, endogenous ROS levels increase. The authors surveyed cell growth and survival and rate and type of DNA damage, such as GCRs, in yeast lacking both tsa1 and a gene involved in either DNA repair or cell cycle control. The analysis identified specific genes in both networks that are required to promote cell survival in the face of increased endogenous ROS. Thus, increased oxidative stress can lead to specific types of DNA damage that, if not repaired by the engagement of multiple pathways, can result in genome instability and changes associated with cancer or aging phenotypes.

M.-E. Huang, R. D. Kolodner, A biological network in Saccharomyces cerevisiae prevents the deleterious effects of endogenous oxidative DNA damage. Mol. Cell 17, 709-720 (2005). [PubMed]

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