Evans J W, Liu X F, Kirchgessner C U, Brown J M
Department of Radiation Oncology, Stanford University School of Medicine, California 94305-5468, USA.
Radiat Res. 1996 Jan;145(1):39-46.
Severe combined immunodeficient (scid) murine cells, which are defective in both repair of DNA double-strand breaks and V(D)J recombination, are deficient in DNA-dependent protein kinase (DNA-PK), a protein which forms an activated complex with the DNA end-binding Ku proteins (p80 and p70) upon association with damaged DNA. Xrs 5 cells are deficient in the Ku p80 protein and also fail to form an active DNA-PK repair complex. Since both scid and xrs cells are defective in the same protein complex, we compared the kinetics of chromosome repair in scid cells to results published previously for xrs 5 cells. C.B-17 cells, scid cells and scid cells complemented with a single human chromosome 8 were irradiated with 6 Gy and allowed to repair from 0-24 h before fusion to HeLa cells for chromosome condensation. Breaks and dicentrics were visualized by fluorescence in situ hybridization. All cells had the same initial amount of chromosome damage, but scid cells had a slower rate of rejoining, more unrejoined breaks and more dicentrics than C.B-17 and scid cells with human chromosome 8. The scid cells appear to respond differently than xrs 5 cells, despite both cells lacking an essential component of the same DNA repair complex.
严重联合免疫缺陷（scid）鼠细胞在DNA双链断裂修复和V（D）J重组方面均存在缺陷，缺乏DNA依赖性蛋白激酶（DNA-PK），该蛋白在与受损DNA结合时会与DNA末端结合的Ku蛋白（p80和p70）形成活化复合物。Xrs 5细胞缺乏Ku p80蛋白，也无法形成活性DNA-PK修复复合物。由于scid和xrs细胞在同一蛋白复合物中存在缺陷，我们将scid细胞中的染色体修复动力学与先前发表的关于Xrs 5细胞的结果进行了比较。将C.B-17细胞、scid细胞和用人8号染色体进行单染色体互补的scid细胞用6 Gy照射，并在与HeLa细胞融合以进行染色体浓缩之前，于0至24小时内进行修复。通过荧光原位杂交观察断裂和双着丝粒。所有细胞的初始染色体损伤量相同，但与C.B-17细胞和带有8号人染色体的scid细胞相比，scid细胞的重新连接速率较慢，未重新连接的断裂更多，双着丝粒也更多。尽管两种细胞都缺乏同一DNA修复复合物的必需成分，但scid细胞的反应似乎与Xrs 5细胞不同。
