Ko M J, Murata K, Hwang D-S, Parvin J D
Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Korea.
Oncogene. 2006 Jan 12;25(2):298-303. doi: 10.1038/sj.onc.1209028.
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.
BRCA1依赖的泛素化活性在源自乳腺细胞的多种组织培养细胞系中调节中心体数量。在这些实验中，我们探究了BRCA1如何抑制中心体扩增。一般来说，多余的中心体可通过三种机制积累：（1）胞质分裂失败以及在细胞周期的重复S期通过复制积累中心体；（2）中心体加倍许可的破坏，使其在细胞周期的不适当时间进行复制；或（3）中心体碎片化。在本研究中，我们发现抑制BRCA1会导致中心粒过早分离和再复制。通过在由于BRCA1抑制导致中心体扩增之前将细胞阻滞在早期S期，然后再释放，我们发现抑制BRCA1会在细胞分裂前的S期末期和G2/M期之间导致中心体扩增。这些结果表明，在这些细胞系中，正常的BRCA1功能对于防止有丝分裂前中心粒分离和中心体再复制至关重要。
