Enzymatic Processing of Radiation-Induced Free Radical Damage in DNA

A significant fraction of DNA damage produced by ionizing radiation comes from free radicals generated during the radiolysis of water, that is, by indirect effects. The hydroxyl radical, the principal damaging species, produces single-strand breaks and a plethora of base and sugar lesions that can be cytotoxic or mutagenic. Free radical-induced DNA damage is repaired by an efficient and ubiquitous process called "base excision repair" which is composed of either three or four enzymatic steps, depending on the initial lesion. The result is an intact DNA molecule with a short repair patch size. If, however, multiply damaged sites similar to those produced by ionizing radiation are processed by base excision repair, a double-strand break can result if the opposing lesions are more than three nucleotides apart. Because base excision repair evolved to protect the genome from endogenous damages, the proteins involved are highly conserved from bacteria to humans, not only at the functional level, but at the level of amino acid sequence.