Repair and genetic consequences of endogenous DNA base damage in mammalian cells.
Living organisms dependent on water and oxygen for their existence face the major challenge of faithfully maintaining their genetic material under a constant attack from spontaneous hydrolysis and active oxygen species and from other intracellular metabolites that can modify DNA bases. Repair of endogenous DNA base damage by the ubiquitous base-excision repair pathway largely accounts for the significant turnover of DNA even in nonreplicating cells, and must be sufficiently accurate and efficient to preserve genome stability compatible with long-term cellular viability. The size of the mammalian genome has necessitated an increased complexity of repair and diversification of key enzymes, as revealed by gene knock-out mouse models. The genetic instability characteristic of cancer cells may be due, in part, to mutations in genes whose products normally function to ensure DNA integrity.