Barnes Deborah E, Lindahl Tomas
Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK.
Annu Rev Genet. 2004;38:445-76. doi: 10.1146/annurev.genet.38.072902.092448.
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.
依赖水和氧气生存的生物面临着一项重大挑战，即在自发水解、活性氧物种以及其他能够修饰DNA碱基的细胞内代谢物的持续攻击下，忠实地维护其遗传物质。普遍存在的碱基切除修复途径对内源DNA碱基损伤的修复在很大程度上解释了即使在非复制细胞中DNA也有显著的更新，并且这种修复必须足够准确和高效，以维持与细胞长期生存能力相兼容的基因组稳定性。基因敲除小鼠模型显示，哺乳动物基因组的大小使得修复的复杂性增加，关键酶也出现了多样化。癌细胞的遗传不稳定性特征可能部分归因于其产物通常起到确保DNA完整性作用的基因发生突变。
