Regulated HsSAS-6 levels ensure formation of a single procentriole per centriole during the centrosome duplication cycle
Regulated HsSAS-6 levels ensure formation of a single procentriole per centriole during the centrosome duplication cycle
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DOI：
10.1016/j.devcel.2007.07.004
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发表时间：
2007-08-01
影响因子：
11.8
通讯作者：
Goenczy, Pierre
中科院分区：
文献类型：
--
作者：
Strnad, Petr;Leidel, Sebastian;Goenczy, Pierre
中心体复制包括在每个中心粒旁边形成单个前中心粒，每个细胞周期一次。控制前中心粒形成的机制和限制每个中心粒发生一次事件的机制尚不清楚。在这里，我们发现HsSAS-6对于前中心孔的形成是必需的，并且在前中心孔形成开始时，它不对称地定位在中心粒旁边。HsSAS-6水平在细胞周期中振荡，蛋白质在有丝分裂中被降解，并在下一个G1结束时再次开始积累。我们的研究结果表明APC（Cdh1）靶向HsSAS-6被26S蛋白酶体降解。重要的是，我们证明增加的HsSAS-6水平促进每个中心粒形成一个以上的前中心粒。因此，调控的HsSAS-6水平通常可以确保每个中心粒在每个细胞周期内种子形成单个前中心粒，从而在驱动中心体复制周期和确保基因组完整性方面发挥基础性作用。
Centrosome duplication involves the formation of a single procentriole next to each centriole, once per cell cycle. The mechanisms governing procentriole formation and those restricting its occurrence to one event per centriole are poorly understood. Here, we show that HsSAS-6 is necessary for procentriole formation and that it localizes asymmetrically next to the centriole at the onset of procentriole formation. HsSAS-6 levels oscillate during the cell cycle, with the protein being degraded in mitosis and starting to accumulate again at the end of the following G1. Our findings indicate that APC(Cdh1) targets HsSAS-6 for degradation by the 26S proteasome. Importantly, we demonstrate that increased HsSAS-6 levels promote formation of more than one procentriole per centriole. Therefore, regulated HsSAS-6 levels normally ensure that each centriole seeds the formation of a single procentriole per cell cycle, thus playing a fundamental role in driving the centrosome duplication cycle and ensuring genome integrity.