Germline mutations in the Breast cancer associated gene 1 (BRCA1) predispose women to breast and ovarian cancers. BRCA1 is involved in many cellular processes, including DNA repair and centrosome regulation. Defects in the regulatory mechanisms of centrosomes and DNA repair result in defective mitosis, 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 the DNA repair pathway have been extensively studied, the mechanism of centrosome 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. These findings suggest that OLA1 plays a role in centrosome duplication and functions as a tumor suppressor together with BRCA1.

To analyze the further functions of BRCA1 and its related proteins, we perform cytological analyses, analyses using genetically modified mice, and analyses of clinical specimens. These researches will contribute to the further understanding of carcinogenesis and to the development novel cancer therapies

Fig. 1 Centrosome amplification by knockdown of OLA1.
Fig. 2 Accumulation of BRCA1 at the sites of DNA damage.