Surviving an Oxygen Atmosphere: DNA Damage and Repair.

Abstract

As a consequence of life's coexistence with the reactive diradical O(2), cells have adapted biochemical defense mechanisms for protection from oxidative damage. Nevertheless, it is estimated that each cell's genomic DNA undergoes thousands of oxidative hits per day, and even more under conditions of stress. Unrepaired oxidative damage to DNA leads to mutations that underlie cancer, aging and neurological disease. Recent studies have helped unravel the oxidation chemistry of the DNA bases, and the myriad biochemical responses of DNA processing enzymes that battle against mutation. On the positive side, oxidative damage to nucleobases may accelerate the evolution of genomes and could have played a role in the ancestry of redox-active nucleoside cofactors as well as the adaptation of early life to changes in the environment.