Tessitore Alessandra, Biordi Leda, Flati Vincenzo, Toniato Elena, Marchetti Paolo, Ricevuto Enrico, Ficorella Corrado, Scotto Luigi, Giannini Giuseppe, Frati Luigi, Masciocchi Carlo, Tombolini Vincenzo, Gulino Alberto, Martinotti Stefano
Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy.
Genes Chromosomes Cancer. 2003 Feb;36(2):198-204. doi: 10.1002/gcc.10145.
Alterations of the NBS1 gene are responsible for Nijmegen breakage syndrome (NBS), which is characterized by chromosomal instability, radiosensitivity, and cancer predisposition. NBS1 protein (Nibrin) is part of a molecular complex (NBS1- MRE11A-RAD50) that is functionally involved in DNA double-strand-break repair. Defects in recombination or in repair mechanisms at the level of DNA breakage can lead to chromosomal aberrations, genetic instability, as well as cancer predisposition syndromes (i.e., NBS, ataxia-telangiectasia, Bloom syndrome). In this study, we examined 20 cancer cell lines to evaluate the potential involvement of NBS1 in tumoral pathogenesis. Three different mutations, generating truncated or aberrant NBS1 transcripts, were identified at the level of NBS1 mRNA. In addition, two shorter NBS1 protein variants were detected in two cell lines. These data suggest a possible involvement of NBS1 in tumor development.
NBS1基因的改变是尼曼-匹克氏症候群（NBS）的病因，其特征为染色体不稳定、辐射敏感性和癌症易感性。NBS1蛋白（Nibrin）是一个分子复合物（NBS1-MRE11A-RAD50）的一部分，该复合物在功能上参与DNA双链断裂修复。DNA断裂水平上的重组或修复机制缺陷可导致染色体畸变、基因不稳定以及癌症易感性综合征（即NBS、共济失调毛细血管扩张症、布卢姆综合征）。在本研究中，我们检测了20种癌细胞系，以评估NBS1在肿瘤发病机制中的潜在作用。在NBS1 mRNA水平上鉴定出三种不同的突变，这些突变产生截短的或异常的NBS1转录本。此外，在两个细胞系中检测到两种较短的NBS1蛋白变体。这些数据表明NBS1可能参与肿瘤发展。
