| Research Abstract |
BRCA1 and BRCA2 were identified as a responsible gene of hereditary breast cancers, and presymptomatic diagnosis demonstrates big power clinically. It is thought that BRCA1 and BRCA2 are caretaker type antioncogenes which work to genome stabilization. Then, we focused on BRCA2, and tried to identify the molecules combined with the BRCA2 protein, and to elucidate the physiological function of BRCA2 based on the meaning of the signal transduction. It is thought that this research greatly contributes to the understanding of the meaning of the signal transduction borne by the target molecule, i. e., the mechanism of breast carcinogenesis.
We showed that two or more nuclear localization signals exist in C terminal of BRCA2, and nuclear export signals are among these. We presumed they functioned integrative and controlled subcellular localization of BRCA2. Moreover, it was shown clearly that Rad51 combines with BRCA2, and BRCA is participating in the double strand break repair of DNA. On the other hand, BRCA2 protein is combined with cytoskeletons, such as myosin, plectin, actinin, and γ-tubulin. BRCA2 is distributed in the nucleus and also around the nucleus toward the centrosome in the cell of G1-S, and colocalizing with γ-tubulin gradually in G2-M. It exists as phosphorylated protein around the chromosomes at M stage. From these results, it was supposed that subcellular localization of BRCA2 differed with each stage of cell cycle, and BRCA2 protein was carrying out the important work in cytokinesis. Furthermore, it identified that TRAF1 and Tax binding protein interacted with BRCA2, and a possibility that BRCA2 would control the apoptosis through NF-kappa B was shown. Taken together, BRCA2 is considered to have functions of DNA damage repair, cytokinesis regulation, and apoptosis control, and to function on homeostasis comprehensively.
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