Nordstrand L M, Ringvoll J, Larsen E, Klungland A
Centre for Molecular Biology and Neuroscience and Institute of Medical Microbiology, Rikshospitalet-Radiumhospitalet HF, University of Oslo, N-0027 Oslo, Norway.
Neuroscience. 2007 Apr 14;145(4):1309-17. doi: 10.1016/j.neuroscience.2006.10.059. Epub 2007 Jan 9.
Six major pathways for DNA repair have been identified. These include (1) DNA repair by direct reversal, (2) base excision repair, (3) mismatch repair, (4) nucleotide excision repair, (5) homologous recombination, and (6) non-homologous end-joining. In addition, several other cellular processes influence the response to DNA damage. The generation of gene-targeted organisms is crucial for assessing the relative contribution of single DNA repair proteins and DNA repair pathways in maintaining genome stability. In particular, the accumulation of DNA damage, mutations and cancer in unexposed gene-targeted animals illuminates the spontaneous load of a particular lesion and the relative significance of a single gene in a specific pathway. Strategies for the generation of gene-targeted mice have been available for 15 years and more than 100 different genes relevant to DNA repair have been targeted. This review describes some important progress made toward understanding spontaneous DNA damage and its repair, exemplified through one, or a few, gene-targeted mice from each major DNA repair pathway.
已确定了六种主要的DNA修复途径。这些途径包括：（1）直接逆转DNA修复；（2）碱基切除修复；（3）错配修复；（4）核苷酸切除修复；（5）同源重组；（6）非同源末端连接。此外，其他一些细胞过程也会影响对DNA损伤的反应。生成基因靶向生物体对于评估单个DNA修复蛋白和DNA修复途径在维持基因组稳定性中的相对作用至关重要。特别是，未暴露的基因靶向动物中DNA损伤、突变和癌症的积累揭示了特定损伤的自发负荷以及特定途径中单个基因的相对重要性。生成基因靶向小鼠的策略已经存在了15年，并且已经对100多个与DNA修复相关的不同基因进行了靶向。本综述描述了在理解自发DNA损伤及其修复方面取得的一些重要进展，以来自每个主要DNA修复途径的一种或几种基因靶向小鼠为例进行说明。
