New mutations and protein variants of NBS1 are identified in cancer cell lines.
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.
Tessitore
Alessandra
A
Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy. tessitor@univaq.it
Biordi
Leda
L
Flati
Vincenzo
V
Toniato
Elena
E
Marchetti
Paolo
P
Ricevuto
Enrico
E
Ficorella
Corrado
C
Scotto
Luigi
L
Giannini
Giuseppe
G
Frati
Luigi
L
Masciocchi
Carlo
C
Tombolini
Vincenzo
V
Gulino
Alberto
A
Martinotti
Stefano
S
D000230:Adenocarcinoma / Q000235:genetics; D017398:Alternative Splicing / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D005260:Female; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics; D014407:Tumor Cells, Cultured
D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; D020033:Protein Isoforms