Ku acts in a unique way at the mammalian telomere to prevent end joining
Ku acts in a unique way at the mammalian telomere to prevent end joining
复制标题
DOI：
10.1101/gad.844000
复制
发表时间：
2000-11-15
影响因子：
10.5
通讯作者：
Chen, DJ
中科院分区：
文献类型：
--
作者：
Hsu, HL;Gilley, D;Chen, DJ
端粒是专门的DNA/蛋白质结构，其充当保护帽以防止末端融合事件并区分染色体末端与双链断裂。我们报告说，TRF 1和Ku形成一个复杂的端粒。Ku和TRF 1复合物是一种特异性高亲和力相互作用，如几种体外方法所证明的，并存在于人类细胞中，如通过免疫共沉淀实验所确定的。Ku不直接结合端粒DNA，而是通过与TRF 1的相互作用定位于端粒重复序列。缺乏Ku 80的原代小鼠胚胎成纤维细胞积累了很大比例的端粒融合，这表明Ku在哺乳动物细胞的端粒加帽中起着关键作用。我们建议Ku定位于端粒的内部区域，通过与TRF 1的高亲和力相互作用。因此，Ku以独特的方式作用于端粒以防止末端连接。
Telomeres are specialized DNA/protein structures that act as protective caps to prevent end fusion events and to distinguish the chromosome ends from double-strand breaks. We report that TRF1 and Ku form a complex at the telomere. The Ku and TRF1 complex is a specific high-affinity interaction, as demonstrated by several in vitro methods, and exists in human cells as determined by coimmunoprecipitation experiments. Ku does not bind telomeric DNA directly but localizes to telomeric repeats via its interaction with TRF1. Primary mouse embryonic fibroblasts that are deficient for Ku80 accumulated a large percentage of telomere fusions, establishing that Ku plays a critical role in telomere capping in mammalian cells. We propose that Ku localizes to internal regions of the telomere via a high-affinity interaction with TRF1. Therefore, Ku acts in a unique way at the telomere to prevent end joining.