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52. Complementary DNA Structure of Mouse Nbs1 Gene That Is the Counterpart of Human Nijmegen Breakage Syndrome Gene
Toshiyuki Saito, Naohiko Seki, Atsushi Hattori1, Masumi Abe, Mitsuoki Morimyo, Tada-aki Hori, and Yoichi Matsuda2
(1Aisin Cosmos R&D; 2Nagoya Univ.)
Keywords: Nijmegen breakage syndrome, NBS1, checkpoint, cell cycle
Nijmegen breakage syndrome (NBS) is an autosomal recessive disorder characterized by increased cancer incidence, cell cycle checkpoint defects, and cellular hypersensitivity to ionizing radiation. The NBS responsible gene (NBS1) product associates with Rad50 and Mre11 proteins both of which are highly conserved between yeast and human. Although NBS1 protein shows little homology to any yeast proteins, it is critical for the complex formation that is essential for repair of DNA double-strand breaks by radiation. To elucidate the important structures of the NBS1 protein, we started describing the divergence of the counterparts among different species.
A putative full length cDNA was isolated from a mouse testis cDNA library. The DNA sequencing revealed an 84 kiloDalton protein product composed of 751 amino acid residues. Amino acid sequence comparison between human and mouse NBS1 protein suggested conservation of two regions in the amino terminal (approximately 350 amino acids) and carboxy terminal half (110). A possible nuclear localization signal was found in the extreme carboxy terminal of the protein. Polymorphisms causing amino acid substitutions have been identified near the amino terminal of the mouse Nbs1 protein.
