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Inhibition of BRCA1 in breast cell lines causes the centrosome duplication cycle to be disconnected from the cell cycle

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.

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Acknowledgements

We thank Dr JL Salisbury for the plasmid expressing GFP-centrin2. This work was supported by a BK21 Research Fellowship from the Ministry of Education, Republic of Korea (MJK) and a Grant CA90281 from the National Cancer Institute (JDP).

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Correspondence to J D Parvin.

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Ko, M., Murata, K., Hwang, DS. et al. Inhibition of BRCA1 in breast cell lines causes the centrosome duplication cycle to be disconnected from the cell cycle. Oncogene 25, 298–303 (2006). https://doi.org/10.1038/sj.onc.1209028

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  • DOI: https://doi.org/10.1038/sj.onc.1209028

Keywords

  • BRCA1
  • centrosome
  • cell cycle
  • breast cancer

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