Centrosome number is controlled by a centrosome-intrinsic block to reduplication

Centrosome number is controlled by a centrosome-intrinsic block to reduplication
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DOI:
10.1038/ncb993
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发表时间:
2003-06-01
影响因子:
21.3
通讯作者:
Stearns, T
Stearns, T
中科院分区:
生物学1区
文献类型:
--
作者:
Wong, C;Stearns, T

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中心体在S期复制一次。为了确定中心体复制是否存在障碍,我们使用了细胞融合实验来比较未复制的G1中心体和最近复制的G2中心体的复制潜力。通过融合不同细胞周期阶段的细胞,我们发现G2中心体在支持中心体复制的细胞环境中无法复制。此外,G2细胞质不抑制融合细胞的中心体复制,这表明阻止复制是中心体固有的,而不是细胞质。为了测试潜在的机制,我们通过融合细胞和去核的细胞质创造了具有两个中心体的单核G1细胞。两个中心体重复,表明阻断不受中心体:核的比例控制。我们还发现,在长时间的S期停滞过程中,人的原代细胞对中心体数量有严格的控制,并且在转化的细胞中这种控制被部分取消。这表明中心体复制的控制和基因组稳定性的维持之间存在联系。
The centrosome duplicates once in S phase. To determine whether there is a block in centrosome reduplication, we used a cell fusion assay to compare the duplication potential of unduplicated G1 centrosomes and recently duplicated G2 centrosomes. By fusing cells in different cell cycle stages, we found that G2 centrosomes were unable to reduplicate in a cellular environment that supports centrosome duplication. Furthermore, G2 cytoplasm did not inhibit centrosome duplication in fused cells, indicating that the block to reduplication is intrinsic to the centrosomes rather than the cytoplasm. To test the underlying mechanism, we created mononucleate G1 cells with two centrosomes by fusing cells with enucleated cytoplasts. Both centrosomes duplicated, indicating that the block is not controlled by centrosome: nucleus ratio. We also found that human primary cells have tight control over centrosome number during prolonged S-phase arrest and that this control is partially abrogated in transformed cells. This suggests a link between the control of centrosome duplication and maintenance of genomic stability.