|Professor||Natsuko CHIBA, MD, PhD|
|Assistant Professor||Yuki YOSHINO, MD, PhD|
|Technical Assistant||Satoko AOKI|
|Secretarial Assistant||Yukiko KOMIYA|
The Department of Cancer Biology focuses on germline mutations in breast cancers associated with gene 1 (BRCA1) in women who are predisposed to breast and ovarian cancers. BRCA1 is involved in many cellular processes including DNA repair and centrosome regulation, and defects in the regulatory mechanisms of centrosome and DNA repair result in defective mitoses, chromosome segregation errors, and the accumulation of DNA damage. These are significant sources of genome instability, a hallmark of cancer.
Although the functions of BRCA1 in DNA repair pathway have been extensively studied, the mechanism of centrosome/mitotic regulation by BRCA1 is largely unknown. Recently, we identified a novel BRCA1-related protein, Obg–like ATPase 1 (OLA1), which functions in centrosome regulation together with BRCA1. The breast cancer-derived OLA1 mutation does not bind to BRCA1 and fails to rescue the OLA1 knockdown-induced centrosome amplification. The familial breast cancer-derived BRCA1 mutation I42V abrogates the binding of BRCA1 to OLA1. To analyze the further functions of BRCA1 and its related proteins, we perform cytological analyses, analyses using genetically modified mice, and analyses of clinical specimen. These researches will contribute to the further understanding the carcinogenesis and developing the novel cancer therapy.
•Regulatory mechanism of cell division by breast cancer-related molecules.
•Response of tumor suppressor molecules to DNA damage.
•Regulatory mechanism of genome integrity.