Pathology Unit, Mater Salutis Hospital, Azienda Unità Locale Socio Sanitaria (AULSS) 9 'Scaligera', Verona, Italy.
Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), Deutsches Krebsforschungszentrum (DKFZ)-ZMBH Allianz, Heidelberg, Germany; Heidelberg Biosciences International Graduate School (HBIGS), Universität Heidelberg, Heidelberg, Germany.
Trends Mol Med. 2020 Apr;26(4):380-393. doi: 10.1016/j.molmed.2020.01.011. Epub 2020 Feb 18.
Centrosome cohesion, the joining of the two centrosomes of a cell, is increasingly appreciated as a major regulator of cell functions such as Golgi organization and cilia positioning. One major element of centrosome cohesion is the centrosome linker that consists of a growing number of proteins. The timely disassembly of the centrosome linker enables centrosomes to separate and assemble a functional bipolar mitotic spindle that is crucial for maintaining genomic integrity. Exciting new findings link centrosome linker defects to cell transformation and genetic disorders. We review recent data on the molecular mechanisms of the assembly and disassembly of the centrosome linker, and discuss how defects in the proper execution of these processes cause DNA damage and genomic instability leading to disease.
中心体黏合,即细胞两个中心体的连接,越来越被认为是调节高尔基体组织和纤毛定位等细胞功能的主要因素。中心体黏合的一个主要元件是中心体连接蛋白,它由越来越多的蛋白质组成。中心体连接蛋白的适时解体使中心体能够分离并组装一个功能性的双极有丝分裂纺锤体,这对于维持基因组完整性至关重要。令人兴奋的新发现将中心体连接蛋白缺陷与细胞转化和遗传疾病联系起来。我们综述了关于中心体连接蛋白组装和解体的分子机制的最新数据,并讨论了这些过程执行不当如何导致 DNA 损伤和基因组不稳定性从而引发疾病。