Interference with BRCA2, which localizes to the centrosome during S and early M phase, leads to abnormal nuclear division
- Department of Genetic Diagnosis, Cancer Institute, Japanese Foundation for Cancer Research, 3-10-6 Ariake, Koto-ku, Tokyo 135-8550 (Japan)
- Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510 (Japan)
- Institute of Medical Science, Tokyo University, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan)
BRCA2 is responsible for familial breast and ovarian cancer, and its gene product is linked to DNA repair and transcriptional regulation. The BRCA2 protein exists mainly in the nucleus. Here, we show that BRCA2 has a centrosomal localization signal (CLS), localizes also to centrosomes during S and early M phases, and may regulate duplication and separation of the centrosomes. Green fluorescent protein (GFP) fused to the CLS peptides from BRCA2 (GFP-CLS) localizes to centrosomes and prevents endogenous BRCA2 from localizing to centrosomes. In addition, expression of GFP-CLS in cells leads to the abnormal duplication and positioning of centrosomes, resulting in the generation of multinuclear cells. These results thus implicate BRCA2 in the regulation of the centrosome cycle, and provide new insight into the aneuploid nature of many breast cancers.
- OSTI ID:
- 20979853
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 355, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2007.01.100; PII: S0006-291X(07)00146-5; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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