A systems biology analysis of protein-protein interactions between yeast superoxide dismutases and DNA repair pathways.

Superoxide dismutases (SODs) are widely distributed in eukaryotic and prokaryotic species and are responsible for O(2)(.-) scavenging and dismutation to H(2)O(2) and O(2). Mutations in the cytoplasmic (Sod1p) or mitochondrial (Sod2p) form of SODs result in aging, neurodegenerative diseases, and carcinogenesis. Diminished activity of SODs leads to reduced activity of DNA repair pathways, and overexpression of SODs in cells defective for DNA repair increases their level of chromatin damage. Unfortunately, little is understood regarding the interplay between SODs and DNA repair proteins and their role in protecting the genome from oxidative damage. To elucidate the association between yeast SODs and DNA repair mechanisms, a systems biology study was performed employing algorithms of literature data mining and the construction of physical protein-protein interactions from large yeast protein databases. The results obtained in this work allow us to draw two models suggesting that yeast SODs act as O(2)(.-) sensors under conditions of redox imbalance, activating and controlling specific DNA repair mechanisms (e.g., recombinational and excision repair pathways), chromatin remodeling, and synthesis of dNTPs.