Genome Stability Group, CR-UK/YCR Sheffield Cancer Research Centre, YCR Institute for Cancer Studies, Department of Oncology, University of Sheffield Medical School, UK.
J Cell Sci. 2012 Oct 15;125(Pt 20):4770-9. doi: 10.1242/jcs.104059. Epub 2012 Jul 13.
The centrosome acts as a centre for microtubule organisation and plays crucial roles in cell polarity, migration, growth and division. Cep131 has recently been described as a basal body component essential for cilium formation, but its function in non-ciliogenic cells is unknown. We identified human Cep131 (also known as AZI1) in a screen for regulators of genome stability. We show that centrosomal localisation of Cep131 is cell-cycle-regulated and requires both an intact microtubule network and a functional dynein-dynactin transport system. Cep131 is recruited to centriolar satellites by PCM1, and localised to the centriolar core region by both pericentrin and Cep290. Depletion of Cep131 results in a reduction in proliferation rate, centriole amplification, an increased frequency of multipolar mitosis, chromosomal instability and an increase in post-mitotic DNA damage. These data therefore highlight the importance of human Cep131 for maintaining genomic integrity.
中心体作为微管组织的中心,在细胞极性、迁移、生长和分裂中起着至关重要的作用。Cep131 最近被描述为纤毛形成所必需的基底体成分,但它在非纤毛细胞中的功能尚不清楚。我们在一个基因组稳定性调节剂的筛选中鉴定了人类 Cep131(也称为 AZI1)。我们表明,Cep131 的中心体定位是细胞周期调控的,需要完整的微管网络和功能性的动力蛋白-动力素运输系统。Cep131 通过 PCM1 被招募到中心粒卫星上,并通过中心粒蛋白和 Cep290 被定位到中心粒核心区域。Cep131 的耗竭导致增殖率降低、中心体扩增、多极有丝分裂的频率增加、染色体不稳定性和有丝分裂后 DNA 损伤增加。因此,这些数据强调了人类 Cep131 对于维持基因组完整性的重要性。