title: Analysis of centrosome localization of BRCA1 and its activity in suppressing centrosomal aster formation.
abstract: BRCA1, a product of a familial breast and ovarian cancer susceptibility gene, localizes to centrosomes and physically interacts with γ-tubulin, a key centrosomal protein for microtubule nucleation and anchoring at centrosomes. Here, we performed a rigorous analysis of centrosome localization of BRCA1, and found that BRCA1 is specifically associated with mother centrioles in unduplicated centrosomes, and daughter centrioles acquire BRCA1 prior to initiation of duplication, and thus duplicated centrosomes are both bound by BRCA1. We further found that BRCA1 suppresses centrosomal aster formation. In addition, we identified a new domain of BRCA1 critical for γ-tubulin binding, which confers not only its localization to centrosomes, but also its activity to suppress centrosomal aster formation.
authors: Department of Environmental Studies, University of Cincinnati, Cincinnati, OH, USA.
authors: Pheruza
authors: P
authors: Tarapore
authors: Kazuhiko
authors: K
authors: Hanashiro
authors: Kenji
authors: K
authors: Fukasawa
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002502:Centrioles / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism*; D005260:Female; D049452:Green Fluorescent Proteins; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D034622:RNA Interference; D034741:RNA, Small Interfering; D008941:Spindle Apparatus / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism*
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D034741:RNA, Small Interfering; D014404:Tubulin; D049452:Green Fluorescent Proteins