Expression of full-length NBS1 protein restores normal radiation responses in cells from nijmegen breakage syndrome patients

被引:33
作者
Ito, A
Tauchi, H
Kobayashi, J
Morishima, K
Nakamura, A
Hirokawa, Y
Matsuura, S
Ito, K
Komatsu, K
机构
[1] Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Radiat Biol, Minami Ku, Hiroshima 7348553, Japan
[2] Hiroshima Univ, Sch Med, Dept Radiol, Minami Ku, Hiroshima 7348551, Japan
关键词
NBS1; Nijmegen breakage syndrome; DNA repair; MRE11;
D O I
10.1006/bbrc.1999.1737
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:716 / 721
页数:6
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