Barnes G, Rio D
Department of Molecular and Cell Biology, University of California, Berkeley 94720-3202, USA.
Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):867-72. doi: 10.1073/pnas.94.3.867.
In mammalian cells, the Ku heterodimer is involved in DNA double-strand-break recognition and repair. We have established in yeast a connection between Ku activity and DNA double-strand-break damage repair, and a connection between Ku activity and commitment to DNA replication. We generated double-stranded DNA breaks in yeast cells in vivo by expressing a restriction endonuclease and have shown that yeast mutants lacking Ku p70 activity died while isogenic wild-type cells did not. Moreover, we have discovered that DNA damage occurs spontaneously during normal yeast mitotic growth, and that Ku functions in repair of this damage. We also observed that mitotically growing Ku p70 mutants have an anomalously high DNA content, suggesting a role for Ku in regulation of DNA synthesis. Finally, we present evidence that Ku p70 function is conserved between yeast, Drosophila, and humans.
在哺乳动物细胞中，Ku异源二聚体参与DNA双链断裂的识别与修复。我们已在酵母中建立了Ku活性与DNA双链断裂损伤修复之间的联系，以及Ku活性与DNA复制起始之间的联系。我们通过表达一种限制性内切核酸酶在酵母细胞体内产生双链DNA断裂，并已表明缺乏Ku p70活性的酵母突变体死亡，而同基因野生型细胞则未死亡。此外，我们发现DNA损伤在正常酵母有丝分裂生长过程中会自发发生，并且Ku在这种损伤的修复中发挥作用。我们还观察到，有丝分裂生长的Ku p70突变体具有异常高的DNA含量，这表明Ku在DNA合成调控中发挥作用。最后，我们提供证据表明，Ku p70的功能在酵母、果蝇和人类之间是保守的。
