Ku70 can translocate to the nucleus independent of Ku80 translocation and DNA-PK autophosphorylation
Ku70 can translocate to the nucleus independent of Ku80 translocation and DNA-PK autophosphorylation
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DOI：
10.1006/bbrc.2000.3567
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发表时间：
2000-10-05
影响因子：
3.1
通讯作者：
Koike, A
中科院分区：
文献类型：
--
作者：
Koike, M;Shiomi, T;Koike, A
Ku在多个核过程中起着重要作用，例如，DNA修复、染色体维持和转录调控。虽然有证据表明Hu的核转位在调节Ku的功能中起关键作用，但其机制尚不清楚。使用定点突变技术，我们在这里证明，Ku 70可以易位到细胞核没有异源二聚体与Ku 80。核定位信号的Ku 70突变体的核积累，保留其与Ku 80的结合能力，减少。另一方面，缺乏与Ku 80结合能力的Ku 70突变体可以易位到细胞核中。当转染时，人Ku 70在仓鼠xrs-6细胞的细胞核内积累，该细胞具有不可检测的DNA-PK活性和Ku 80。DNA-PK磷酸化位点的Ku 70和Ku 80突变体显示正常的异源二聚体化和核转位。这些发现也支持Ku 70可以不依赖于DNA-PK自身磷酸化而易位到细胞核的想法。(C)北京大学出版社.
Ku plays an important role in multiple nuclear processes, e.g., DNA repair, chromosome maintenance, and transcriptional regulation. Although some evidence suggests that the nuclear translocation of Hu plays a key role in regulating the function of Ku, the mechanism is poorly understood. Using the site-directed mutagenesis technique, we demonstrate here that Ku70 can translocate to the nucleus without heterodimerization with Ku80. The nuclear accumulation of Ku70 mutants of the nuclear localization signal, which retained their binding ability with Ku80, was diminished. On the other hand, Ku70 mutants which lacked the ability to bind with Ku80 could translocate to the nuclei. Human Ku70, when transfected, accumulated within the nuclei of hamster xrs-6 cells which had undetectable DNA-PK activity and Ku80. Ku70 and Ku80 mutants of DNA-PK phosphorylation sites showed normal heterodimerization and nuclear translocation. These findings also support the idea that Ku70 can translocate to the nucleus independent of DNA-PK autophosphorylation. (C) 2000 Academic Press.