Kanaar R, Hoeijmakers J H, van Gent D C
Dept of Cell Biology and Genetics, Erasmus University Rotterdam, The Netherlands.
Trends Cell Biol. 1998 Dec;8(12):483-9. doi: 10.1016/s0962-8924(98)01383-x.
DNA double-strand breaks (DSBs) are major threats to the genomic integrity of cells. If not taken care of properly, they can cause chromosome fragmentation, loss and translocation, possibly resulting in carcinogenesis. Upon DSB formation, cell-cycle checkpoints are triggered and multiple DSB repair pathways can be activated. Recent research on the Nijmegen breakage syndrome, which predisposes patients to cancer, suggests a direct link between activation of cell-cycle checkpoints and DSB repair. Furthermore, the biochemical activities of proteins involved in the two major DSB repair pathways, homologous recombination and DNA end-joining, are now beginning to emerge. This review discusses these new findings and their implications for the mechanisms of DSB repair.
DNA双链断裂（DSB）是对细胞基因组完整性的主要威胁。如果处理不当，它们会导致染色体断裂、丢失和易位，可能引发癌变。DSB形成后，细胞周期检查点被触发，多种DSB修复途径可被激活。最近对导致患者易患癌症的尼曼匹克氏症候群的研究表明，细胞周期检查点的激活与DSB修复之间存在直接联系。此外，参与两种主要DSB修复途径（同源重组和DNA末端连接）的蛋白质的生化活性现在也开始显现出来。本综述讨论了这些新发现及其对DSB修复机制的影响。
