DNA repair defect, tumorigensis, and hereditary breast cancer gene Brca2 -Studies in vitro and in vivo, and association with Rad51.

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To establish the bases of developing new methods for prevention, diagnosis, and therapy of breast cancer , we investigated in vitro and invivo functions of the Brca2 and other tumor associated genes. Especially, researches for the significance of the interaction of Brca2 and Rad51, application of Brca2 analysis in veterinary medicine, and roles IkB MAIL were carried out.1. Cloning and mutation analysis of canine Brca2Full length (about 10 kbp) of the cDNA for canine Brca2 was cloned and sequenced. For mutation analysis, DNA fragments were obtained by PCR and used for protein truncation tests.2. Cloning and expression of feline Brca2Full length (about 10 kbp) of the cDNA for feline Brca2 was cloned and sequenced. Expression of feline Brca2 was confirmed in mamnary gland.3. Interaction of Brca2 and Rad51Interaction of C-terminus of canine Brca2 with Rad51 was demonstrated by yeast two-hybrid assay. Transactivation activity of canine Brca2 was also demonstrated.4. Characterization of a novel IkB protein, MAILWe cloned, sequenced, and analyzed the expression of the MAIL gene encoding a novel IkB protein.