Expression of full-length NBS1 protein restores normal radiation responses in cells from nijmegen breakage syndrome patients
Expression of full-length NBS1 protein restores normal radiation responses in cells from nijmegen breakage syndrome patients
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DOI：
10.1006/bbrc.1999.1737
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发表时间：
1999-11-30
影响因子：
3.1
通讯作者：
Komatsu, K
中科院分区：
文献类型：
--
作者：
Ito, A;Tauchi, H;Komatsu, K
奈梅根断裂综合征(NBS)的细胞表现出多种表型，如染色体不稳定，对电离辐射所致的细胞杀伤超敏，以及可能的细胞周期检查点异常。NBS1是一种在NBS患者中突变的基因，似乎编码了一种可能的修复蛋白，该蛋白可能形成能够检测DNA双链断裂的传感器样分子复合体的焦点，然而，它没有信号转导DNA损伤的激活域。在这里，我们报告了NBS1基因在NBS细胞中的稳定表达，导致了细胞核内完全恢复了病灶的形成，并使正常细胞在照射后存活。照射后观察到的延长的G2阻滞期也被NBS1的表达取消，这进一步证实了在NBS细胞中G2检查点被取消。这些结果表明，NBS1蛋白的缺陷可能是NBS表型的唯一原因，并且NBS1可能与另一种蛋白(S)相互作用，产生整个NBS的表型表达。(C)1999年学术出版社。
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. (C) 1999 Academic Press.