Ito A, Tauchi H, Kobayashi J, Morishima K, Nakamura A, Hirokawa Y, Matsuura S, Ito K, Komatsu K
Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
Biochem Biophys Res Commun. 1999 Nov 30;265(3):716-21. doi: 10.1006/bbrc.1999.1737.
Cells from Nijmegen breakage syndrome (NBS) display multiple phenotypes, such as chromosomal instability, hypersensitivity to cell killing from ionizing radiation, and possibly abnormal cell cycle checkpoints. NBS1, a gene mutated in NBS patients, appears to encode a possible repair protein, which could form the foci of a sensor-like molecular complex capable of detecting DNA double strand breaks, however, it has no kinase domain for signaling DNA damage. Here, we report that the stable expression of NBS1 cDNA in NBS cells after transfection results in the complete restoration of foci formation in the nucleus, and in normal cell survival after irradiation. The prolonged G2 block observed after irradiation was also abolished by expression of NBS1, providing additional confirmation that the G2 checkpoint is abrogated in NBS cells. These results suggest that a defective NBS1 protein could be the sole cause of the NBS phenotype, and that NBS1 likely interacts with another protein(s) to produce the entire range of NBS phenotypic expression.
尼曼-匹克氏病C型（NBS）患者的细胞表现出多种表型，如染色体不稳定、对电离辐射导致的细胞杀伤高度敏感，以及可能存在异常的细胞周期检查点。NBS1是NBS患者中发生突变的一个基因，它似乎编码一种可能的修复蛋白，该蛋白可能形成一种类似传感器的分子复合物的病灶，能够检测DNA双链断裂，然而，它没有用于信号传导DNA损伤的激酶结构域。在此，我们报告转染后NBS细胞中NBS1 cDNA的稳定表达导致细胞核中病灶形成的完全恢复，以及照射后正常的细胞存活。照射后观察到的延长的G2期阻滞也因NBS1的表达而消除，这进一步证实了NBS细胞中的G2检查点被废除。这些结果表明，有缺陷的NBS1蛋白可能是NBS表型的唯一原因，并且NBS1可能与另一种或多种蛋白相互作用以产生NBS表型表达的整个范围。
