Caldecott K W
School of Biological Sciences, G.38 Stopford Building, University of Manchester, Oxford Road, M13 9PT, UK.
Bioessays. 2001 May;23(5):447-55. doi: 10.1002/bies.1063.
The genetic stability of living cells is continuously threatened by the presence of endogenous reactive oxygen species and other genotoxic molecules. Of particular threat are the thousands of DNA single-strand breaks that arise in each cell, each day, both directly from disintegration of damaged sugars and indirectly from the excision repair of damaged bases. If un-repaired, single-strand breaks can be converted into double-strand breaks during DNA replication, potentially resulting in chromosomal rearrangement and genetic deletion. Consequently, cells have adopted multiple pathways to ensure the rapid and efficient removal of single-strand breaks. A general feature of these pathways appears to be the extensive employment of protein-protein interactions to stimulate both the individual component steps and the overall repair reaction. Our current understanding of DNA single-strand break repair is discussed, and testable models for the architectural coordination of this important process are presented.
活细胞的遗传稳定性不断受到内源性活性氧和其他基因毒性分子的威胁。特别具有威胁性的是，每个细胞每天都会出现数千个DNA单链断裂，这些断裂既直接源于受损糖的分解，也间接源于受损碱基的切除修复。如果不进行修复，单链断裂在DNA复制过程中可能会转化为双链断裂，从而可能导致染色体重排和基因缺失。因此，细胞采用了多种途径来确保快速有效地去除单链断裂。这些途径的一个普遍特征似乎是广泛利用蛋白质-蛋白质相互作用来刺激各个组成步骤和整体修复反应。我们讨论了目前对DNA单链断裂修复的理解，并提出了可测试的该重要过程的结构协调模型。
