Morency Eric, Sabra Mirna, Catez Frédéric, Texier Pascale, Lomonte Patrick
Viral Silencing and Centromeric Instability Team, Université Lyon 1, Lyon F-69003, France.
J Cell Biol. 2007 Jun 4;177(5):757-68. doi: 10.1083/jcb.200612107.
Interphase centromeres are crucial domains for the proper assembly of kinetochores at the onset of mitosis. However, it is not known whether the centromere structure is under tight control during interphase. This study uses the peculiar property of the infected cell protein 0 of herpes simplex virus type 1 to induce centromeric structural damage, revealing a novel cell response triggered by centromere destabilization. It involves centromeric accumulation of the Cajal body-associated coilin and fibrillarin as well as the survival motor neuron proteins. The response, which we have termed interphase centromere damage response (iCDR), was observed in all tested human and mouse cells, indicative of a conserved mechanism. Knockdown cells for several constitutive centromere proteins have shown that the loss of centromeric protein B provokes the centromeric accumulation of coilin. We propose that the iCDR is part of a novel safeguard mechanism that is dedicated to maintaining interphase centromeres compatible with the correct assembly of kinetochores, microtubule binding, and completion of mitosis.
间期着丝粒是有丝分裂开始时动粒正确组装的关键结构域。然而，目前尚不清楚着丝粒结构在间期是否受到严格调控。本研究利用单纯疱疹病毒1型感染细胞蛋白0的特殊性质诱导着丝粒结构损伤，揭示了由着丝粒不稳定引发的一种新型细胞反应。它涉及到与卡哈尔体相关的卷曲螺旋蛋白和纤维蛋白以及生存运动神经元蛋白在着丝粒处的积累。我们将这种反应称为间期着丝粒损伤反应（iCDR），在所有测试的人类和小鼠细胞中均有观察到，表明这是一种保守机制。对几种组成型着丝粒蛋白进行敲低的细胞显示，着丝粒蛋白B的缺失会引发卷曲螺旋蛋白在着丝粒处的积累。我们认为，iCDR是一种新型保护机制的一部分，该机制致力于维持间期着丝粒与动粒的正确组装、微管结合以及有丝分裂的完成相兼容。
