1. ¹Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Korea
2. ²Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA

Correspondence: Dr JD Parvin, Department of Pathology, Brigham and Women's Hospital, NRB 630, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. E-mail: jparvin@rics.bwh.harvard.edu

³Current address: Department of Anatomy, University of Cambridge, Cambridge, UK.

Received 17 May 2005; Revised 20 July 2005; Accepted 20 July 2005; Published online 19 September 2005.

Abstract

BRCA1-dependent ubiquitination activity regulates centrosome number in several tissue culture cell lines derived from breast cells. In these experiments, we asked how BRCA1 inhibits centrosome amplification. In general, supernumerary centrosomes can accumulate by three mechanisms: (1) failed cytokinesis and the accumulation of centrosomes by duplication in a repeated S-phase of the cell cycle, (2) disruption of the licensing of centrosome doubling such that they duplicate at inappropriate times in the cell cycle, or (3) fragmentation of the centrosomes. In this study, we found that inhibition of BRCA1 caused premature separation of centrioles and reduplication. By blocking cells in early S-phase before centrosome amplification secondary to BRCA1 inhibition could occur and then releasing, we found that inhibition of BRCA1 caused centrosome amplification between late S-phase and G2/M before the cell divided. These results suggest that normal BRCA1 function is critical in these cell lines to prevent centriole separation and centrosome reduplication before mitosis.